2 hours agoBBCA transformational gene therapy that reverses the bleeding disorder haemophilia B is being made available on the NHS.

According to Bloomberg News, a document posted briefly to the court’s website suggested a majority of the justices would reinstate a lower-court ruling that paused the state’s near-total abortion ban.The Supreme Court seems poised to temporarily allow emergency abortions in Idaho when a woman’s health is at risk, according to a copy of what appeared to be the opinion that showed up briefly on the court’s website on Wednesday.The unsigned opinion dismissed the case on procedural grounds, stating that the court, for now, would not address the merits of the dispute, according to the 22-page document, which was published by Bloomberg News. Such a decision would reinstate a ruling by a lower federal court that had paused Idaho’s near-total ban on abortion and said hospitals in the state could perform emergency abortions if necessary to protect the health of the mother.The case centers on whether a federal law requiring emergency care for any patient overrides Idaho’s strict abortion ban, which outlaws the procedure with few exceptions unless the woman’s life is in danger.It was unclear whether the document was final, and a spokeswoman for the court said only that a decision in the joined cases, Moyle v. United States and Idaho v. United States, would eventually be released.“The court’s publications unit inadvertently and briefly uploaded a document to the court’s website,” said the spokeswoman, Patricia McCabe. “The court’s opinion in Moyle v. United States and Idaho v. United States will be issued in due course.”We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

AL (immunoglobulin light chain) amyloidosis is a rare disease that often results in progressive organ dysfunction, organ failure and eventual death.
Clonal plasma cells in the bone marrow secrete free light chains into circulation. These light chains are part of immunoglobulins, also called antibodies. But in this disease, light chains misfold and aggregate into amyloid fibrils that deposit in organs and tissues.
In a review article of AL amyloidosis “Systemic Light Chain Amyloidosis,” Vaishali Sanchorawala, MD, director of the Amyloidosis Center at the Chobanian & Avedisian School of Medicine and Boston Medical Center, focused on recent advances in the understanding of pathogenesis, clinical syndromes, risk stratification and therapeutic advances, and looking at future efforts and needs in treatment and research.
“The care of patients with systemic immunoglobulin light chain (AL) amyloidosis has undergone transformative changes, leading to marked, steady progress in outcomes for patients over the past four decades,” Sanchorawala wrote in her review. “Overall survival has improved considerably, yet many unmet needs persist.”
“One of the most important determinants of survival is the severity of cardiac involvement,” said Sanchorawala. The heart is affected in 70 to 80% of patients with AL amyloidosis and cardiac problems are the leading cause of death, but other major organs like kidneys, liver, and peripheral and autonomic nervous systems can also be affected by this disease.
Therapies include those targeting clonal plasma cells, stopping light chain production, and new research into antifibril monoclonal antibodies that accelerate the removal of amyloid deposits from the organs.
“The arsenal of therapeutics for AL amyloidosis is rapidly expanding, offering a promising outlook and emerging triumph over adversity for patients in 2024,” said Sanchorawala. Early diagnosis is critical, and she recommended including evaluation for AL amyloidosis for patients exhibiting a wide range of symptoms and clinical syndromes.
“Despite improvements in the diagnosis and treatment of AL amyloidosis, continued basic and clinical research efforts are needed to brighten the future for patients with this disorder,” said Sanchorawala.

New research led by UCLA Health confirms that both Tai Chi and cognitive behavioral therapy can reduce insomnia in breast cancer survivors but also may provide additional health benefits by reducing inflammation and bolstering anti-viral defenses.
Chronic insomnia is one of the most prominent symptoms experienced among cancer survivors and poses significant health concerns, including the risk of inflammatory disease that could increase the risk of cancer recurrence.
About 30% of breast cancer survivors are reported to have insomnia, which is twice the rate of the general population. While previous research has shown cognitive behavioral therapy and mind-body interventions such as Tai Chi are effective at treating insomnia among breast cancer survivors, less is known about their effectiveness in reversing inflammation caused by insomnia.
The new study, published in the journal Brain, Behavior, and Immunity this month, compared the two therapies among 90 breast cancer survivors using blood samples over 15 months to analyze changes in inflammation biomarkers.
Researchers found Tai Chi specifically led to more significant, sustained reduction in inflammation among participants compared to cognitive behavioral therapy. By comparison, cognitive behavioral therapy participants had greater anti-viral gene transcripts, which potentially improve the body’s defenses against infections.
“Tai Chi can be readily provided in community settings, with minimal cost, and can treat insomnia in adults, older adults and cancer survivors,” said Dr. Michael Irwin, the study’s lead author and professor at UCLA Health’s Department of Psychiatry and Biobehavioral Sciences. “Further, Tai Chi, as compared to cognitive behavioral therapy, has additional advantage in reducing inflammation in breast cancer survivors.”
The study relied on blood samples taken from breast cancer survivors from a 2017 study, also led by Irwin, that examined the effectiveness of Tai Chi versus cognitive behavioral therapy in insomnia treatment and remission. Blood samples were collected from 2008 to 2012 from the 90 participants from the Los Angeles area prior to treatment and at 2-, 3-, 6- and 15-month intervals. Researchers evenly split participants to either undergo weekly Tai Chi or cognitive behavioral therapy sessions lasting 120 minutes for a three-month period.

Analyses of the blood samples taken at the 15-month interval showed Tai Chi participants had reduced cellular and genomic markers of inflammation, specifically in plasma interleukin-6, TLR-4 stimulated monocyte production of inflammatory cytokines and inflammatory transcriptional profiles. Blood samples from the cognitive behavioral therapy showed greater increases in anti-viral gene transcripts.
“Effective treatment of insomnia has potent impacts on the immune system,” said Irwin, who also directs UCLA Health’s Mindful Awareness Research Center. “Tai Chi preferentially reduces inflammation as compared to cognitive behavioral therapy, whereas cognitive behavioral therapy preferentially improves antiviral viral immunity or resistance to infectious disease. Further research that examines the combined benefit of Tai Chi and cognitive behavioral therapy is needed, especially in cancer survivors who are at risk for inflammatory disorder as well as infectious disease.”
There were several limitations in the study and further studies are needed to test the effectiveness of these therapies across different populations. The participants were primarily white, older (ages ranging from 42-83) and had higher education. The study also excluded participants who had coexisting medical conditions. Changes in participants’ sleep-wake cycle and alignment with circadian rhythms may have also yielded these inflammatory health benefits. Additionally, access to Tai Chi may be limited in some communities and requires ongoing practice for several days per week as compared to cognitive behavioral therapy.
Ongoing research is examining the trajectories of inflammatory activation and accelerated aging in breast cancer survivors, as compared to non-cancer control women, which will identify behavioral and biological targets for prevention of depression, as well and other morbidities in cancer survivors.

Moderate levels of physical activity and fitness may be linked to a reduced risk of amyotrophic lateral sclerosis (ALS) later in life, according to a new studypublished in the June 26, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study only found an association between physical activity and risk of ALS in male participants, not female participants.
ALS is a rare, progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. People with ALS lose the ability to initiate and control muscle movement, which often leads to total paralysis and death. The average life span after diagnosis is two to five years.
“The diagnosis of prominent athletes with ALS at young ages has sparked the uncomfortable idea that higher physical activity could be tied to developing ALS,” said studyauthor Anders Myhre Vaage, MD, of Akershus University Hospital in Norway. “There have been conflicting findings on levels of physical activity, fitness and ALS risk. Our study found that for men, living a more active lifestyle could be linked to a reduced risk of ALS more than 30 years later.”
For the study, researchers looked at 373,696 people in Norway with an average age of 41. They were followed for an average of 27 years.
Of the total participants, 504 people developed ALS. Of those who developed ALS, 59% were male participants.
Participants recorded their level of physical activity for the past year into one of four categories: sedentary; a minimum of four hours per week of walking or cycling; a minimum of four hours per week of recreational sports or heavy gardening; or participation in hard training or sports competitions regularly, several times a week. Due to few participants with the highest level of physical activity, researchers combined the third and fourth categories into one high activity group.
Researchers found that of the 41,898 male participants that had the highest level of physical activity, 63 developed ALS; of the 76,769 male participants with the intermediate level of physical activity, 131 developed ALS; and of the 29,468 male participants with the lowest level of physical activity, 68 developed ALS.

After adjusting for other factors that could affect the risk of ALS, such as smoking and body mass index, researchers found that for male participants, when compared to those with the lowest level of physical activity, those with moderate levels of physical activity had a 29% lower risk of ALS and those with high levels of physical activity had a 41% lower risk of ALS.
Researchers also looked at resting heart rate. Men in the lowest of four categories of resting heart rate, which indicates good physical fitness, had a 32% reduced risk of ALS compared to those with higher resting heart rates.
“Our findings show that, for men, not only do moderate to high levels of physical activity and fitness not increase the risk of ALS, but that it may be protective against the disease,” Myhre Vaage said. “Future studies of the connection between ALS and exercise are needed to consider sex differences and higher or professional athlete physical activity levels.”
A limitation of the study was that the physical activity questionnaire was completed only at one specific time during the study, so it may not have captured the participants’ exercise levels over the nearly 30-year span of the study.

A drug used to prevent migraine may also be effective in people with migraine who experience rebound headaches, according to a new study published in the June 26, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology.
People with chronic migraine who overused pain medication had fewer monthly migraine and headache days and fewer days using pain medication when taking the migraine prevention drug atogepant.
“There is a high prevalence of pain medication overuse among people with migraine as they try to manage what are often debilitating symptoms,” said study author Peter J. Goadsby, MD, PhD, of King’s College London and a member of the American Academy of Neurology. “However, medication overuse can lead to more headaches called rebound headaches, so more effective preventive treatments are needed. Our findings are encouraging, suggesting atogepant may help reduce the need for pain medication among people with chronic migraine.”
The study involved 755 participants who had chronic migraine, defined as having 15 or more headache days per month with eight or more qualifying as migraine.
Of this group, 66% met the criteria for medication overuse defined as taking pain medications such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen for 15 or more days in a month, triptans or ergots for 10 or more days a month, or any combination for 10 or more days.
At the start of the study, average monthly migraine days ranged from 18 to 19, and average monthly pain medication days ranged from 15 to 16.
For 12 weeks, participants were either given 30 milligrams (mg) of atogepant twice daily, 60 mg once daily, or a placebo. Atogepant is a calcitonin gene-related peptide receptor antagonist, or CGRP inhibitor. CGRP is a protein that plays a key role in starting the migraine process.

Participants recorded their migraines and headaches in an electronic diary, noting characteristics including duration and intensity, whether they experienced aura or nausea, and if they took other medications.
Researchers found for participants with medication overuse, those taking atogepant twice daily had an average of three fewer migraine days a month and three fewer headache days when compared to those taking placebo. Those taking the drug once a day had two fewer migraine days a month and two fewer headache days compared to placebo. Both groups also had three fewer days of taking pain medications to treat their symptoms when compared to placebo. Researchers say similar reductions were found among participants without medication overuse.
In those with medication overuse, 45% of those taking the drug twice daily and 42% of those taking it once a day had a 50% or more reduction in average monthly migraine days compared to 25% taking the placebo.
The number of people meeting the criteria for medication overuse also declined by 62% among those taking the drug twice daily and by 52% among those taking it once a day.
“Based on our findings, treatment with atogepant may potentially decrease the risk of developing rebound headache by reducing the use of pain medications,” said Goadsby. “This could lead to an improved quality of life for those living with migraine.”
Goadsby noted more studies are needed to evaluate the long-term safety and effectiveness of atogepant, as well as to assess the potential risk of medication overuse relapse among people with migraine.
A limitation of the study was that participants recorded their headaches and medication use in electronic diaries, so it is possible some participants may not have recorded all information accurately.
The study was funded by AbbVie, the maker of atogepant. Goadsby reported that he received personal fees from AbbVie during the study.

Adults who continuously played organized sports through their youth have fewer symptoms of anxiety and depression than those who never played or those who dropped out, a new study finds.
And those who dropped out of sports had poorer mental health than those who never played at all.
But many more people drop out of youth sports than play continuously until they are 18, said Chris Knoester, senior author of the study and professor of sociology at The Ohio State University.
“If you play and stick with sports, it’s a positive for your mental health, but if you play and drop out it seems to be negative — and most kids drop out,” Knoester said.
The study, published in the Sociology of Sport Journal, showed that most people dropped out of sports because they weren’t having fun or felt they weren’t good enough. That suggests ways youth sports can be improved to help kids, said study lead author Laura Upenieks, assistant professor of sociology at Baylor University.
“Our findings about why kids drop out of organized sports suggests that the current environment is less than ideal for everyone, and that the barriers to participation need to be given greater attention,” Upenieks said.
The study used data from the National Sports and Society Survey, conducted in 2018 and 2019 by Ohio State. It included a sample of 3,931 adults from across the country who answered questions about their sports participation as children and their current anxiety and depression symptoms.

Results showed 35% of the participants did not play organized sports at all, 41% participated and dropped out and 24% participated continuously until age 18.
Those who participated in organized sports continuously while growing up reported lower depressive symptoms and symptoms of anxiety than others.
Those who dropped out had the worst mental health profile, with those who never played in the middle.
Knoester emphasized that most participants didn’t have clinical levels of depression or anxiety, and the differences between the three groups were relatively modest. But the differences still mattered.
By far the most common reason cited for dropping out was “not having fun,” which nearly half of respondents (45%) identified. The next most common reason was feeling like they were not a good player (31%). Other reasons for dropping out were wanting to focus on grades (16%), having a health problem or injury (16%), not being able to afford sports (16%), having an issue with team members (15%) and having an interest in other clubs and activities (14%).
Notably, 8% said they dropped out because they had been abused by a coach.

While dropping out of sports was associated with poorer mental health, “not all reasons for dropping out had the same effects,” Upenieks said.
Interpersonal reasons for dropping out — including not having fun, not getting along with team members and being abused by a coach — were associated with adult depressive and anxiety symptoms.
Those who couldn’t afford sports and sporting equipment also showed poorer mental health.
But those who dropped out in order to focus on grades actually showed lower depressive symptoms, the study found.
“Prioritizing education predicts better mental health as an adult,” Knoester said.
Many previous studies have focused on the impact of playing sports — or not playing — on adult outcomes. But this study is one of the first to look at what happens when youth quit sports, Knoester said, and it shows that persistence in playing is an important issue.
“Unfortunately, it is not a simple story of playing sports is good for kids,” he said. “It is complicated by whether kids stick to playing sports and the reasons why they do stick to it or quit.”
It is easy to see why sports can be good for those who are able to continue with it to adulthood, Upenieks said.
“The longer that youth are exposed to a positive and encouraging sporting environment, the more likely they are to develop habits that are conducive to long-term mental well-being, such as a commitment to regular exercise and collaborating with others as part of a team,” she said.
The fact that so many kids quit shows that organized sports often don’t provide a positive environment. But there are steps adults can take to improve that environment.
For one, sports should be safe for kids. The fact that 8% said they were abused by coaches is particularly alarming, the researchers said.
And the finding that nearly half of kids quit because they weren’t having fun and about a third dropped out because they felt they weren’t good enough should also be a wake-up call, Knoester said.
“We need to improve youth sports so that it supports positive experiences for everyone and makes it more enjoyable,” he said.
While winning is part of sports, it may be that adults overemphasize that aspect and ruin the experience for many young people.
“Most kids are looking to have fun with their friends and support and encourage each other,” Upenieks said. “It doesn’t have to be all serious.”
Knoester added: “Our results suggest that by taking away the fun and making kids feel they aren’t good enough, there could be cascading effects in terms of hurting self-esteem and confidence that could reverberate through to adulthood.”

While the liver is one of the body’s most resilient organs, it is still vulnerable to the ravages of stress and aging, leading to disease, severe scarring and failure. A Duke Health research team now might have found a way to turn back time and restore the liver.
In experiments using mice and liver tissue from humans, the researchers identified how the aging process prompts certain liver cells to die off. They were then able to reverse the process in the animals with an investigational drug.
The finding, which appears in the journal Nature Aging, holds high promise for the millions of people who have some degree of liver damage — livers that are essentially old due to the metabolic stresses of high cholesterol, obesity, diabetes or other factors.
“Our study demonstrates that aging is at least partially reversible,” said senior author Anna Mae Diehl, M.D., the Florence McAlister Distinguished Professor of Medicine at the Duke University School of Medicine. “You are never too old to get better.”
Diehl and colleagues set out to understand how non-alcoholic liver disease develops into a severe condition called cirrhosis, in which scarring can lead to organ failure. Aging is a key risk factor for cirrhosis among those who have been diagnosed with non-alcoholic liver disease, known as metabolic dysfunction-associated steatotic liver disease, or MASLD. One in three adults worldwide have the disease.
Studying the livers of mice, the researchers identified a genetic signature distinct to old livers. Compared to young livers, the old organs had an abundance of genes that were activated to cause degeneration of hepatocytes, the main functioning cells of the liver.
“We found that aging promotes a type of programmed cell death in hepatocytes called ferroptosis, which is dependent on iron,” Diehl said. “Metabolic stressors amplify this death program, increasing liver damage.”
Armed with their genetic signature of old livers, the researchers analyzed human liver tissue and found that the livers of people diagnosed with obesity and MASLD carried the signature, and the worse their disease, the stronger the signal.

Importantly, key genes in the livers of people with MASLD were highly activated to promote cell death through ferroptosis. This gave the researchers a definitive target.
“There are things we can use to block that,” Diehl said.
Again turning to mice, the researchers fed young and old mice diets that caused them to develop MASLD. They then gave half the animals a placebo drug and the other half a drug called Ferrostatin-1, which inhibits the cell death pathway.
Upon analysis after treatment, the livers of the animals given Ferrostatin-1 looked biologically like young, healthy livers — even in the old animals that were kept on the disease-inducing diet.
“This is hopeful for all of us,” Diehl said. “It’s like we had old mice eating hamburgers and fries, and we made their livers like those of young teenagers eating hamburgers and fries.”
Diehl said the team also looked at how the ferroptosis process in the liver impacts the function of other organs, which are often damaged as MASLD progresses. The genetic signature was able to differentiate between diseased and healthy hearts, kidneys and pancreases, indicating that damaged livers amplify ferroptotic stress in other tissues.

“Together, we’ve shown that aging exacerbates non-alcoholic liver disease by creating ferroptic stress, and by reducing this impact, we can reverse the damage,” Diehl said.
In addition to Diehl, study authors include Kuo Du, Liuyang Wang, Ji Hye Jun, Rajesh K. Dutta, Raquel Maeso-Díaz, Seh Hoon Oh and Dennis C. Ko.
The study received funding support from the 2021 AASLD Pinnacle Award, the National Institutes of Health (R01 AA010154, R01 DK077794, R56 DK134334); and Boehringer Ingelheim Pharmaceuticals, Inc.

Fewer Americans age 60 to 74 should receive the shots, the agency concluded, citing reduced risks and a possible neurological side effect.In an unusual move, federal health officials narrowed their recommendations for who should receive the vaccine against the respiratory syncytial virus.The Centers for Disease Control and Prevention advised last year that adults age 60 or older could receive a single lifetime dose of an R.S.V. vaccine, in consultation with their health care providers.On Wednesday, scientific advisers to the agency reframed that guideline. Based on recent safety and effectiveness data, they unanimously recommended that all Americans age 75 and older receive one dose of an R.S.V. vaccine.But for adults 60 to 74 years of age, the panel endorsed vaccination only for those with certain serious conditions, such as chronic heart or lung disease, advanced kidney disease and diabetes with organ damage.The advisers voted not to recommend the vaccine for other adults in this age group, although individuals may still consult with their health care providers to evaluate the risk the infection poses to them.The C.D.C.’s director, Dr. Mandy Cohen, accepted the panel’s recommendations on Wednesday afternoon.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Neuroscientists have discovered how the brain bidirectionally controls sensitivity to threats to initiate and complete escape behaviour in mice. These findings could help unlock new directions for discovering therapies for anxiety and post-traumatic stress disorder (PTSD).
The study, published today in Current Biology, outlines how researchers at the Sainsbury Wellcome Centre at UCL studied a region of the brain called the periaqueductal gray (PAG), which is known to be hyperactive in people with anxiety and PTSD. Their findings show that inhibitory neurons in the PAG constantly fire, which means that their level can be dialled up and down. The team found that this has a direct impact on escape initiation in mice and that the same neurons were also responsible for how long escape lasts.
“Escape behaviour is not fixed — it’s adaptable with experience. Our previous studies have shown that mice become more or less likely to escape depending on their past experience. And so, we wanted to understand how the brain regulates sensitivity to threats as this could have implications for people with anxiety and PTSD where these circuits may be misregulated,” commented Professor Tiago Branco, Group Leader at SWC and corresponding author on the paper.
To study how the brain controls escape behaviour, the team first carried out in vitro recordings from PAG inhibitory neurons (in a dish) to look at their properties. They found that in the absence of input, the PAG inhibitory neurons always fire. They confirmed this finding through in vivo recordings using calcium imaging and head mounted miniature microscopes while mice ran around. The team also performed some connectivity studies in the brain and showed that the PAG inhibitory neurons are directly connected to the excitatory neurons that are known to initiate escape.
“We found that the whole escape network is under direct inhibitory control. When we looked at what happens during escape, we found a group of cells where the activity goes down just before escape. This means that the inhibition is removed so that escape can be initiated. We also found another group of cells where inhibition gradually increases as the animal is escaping and peaks when the animal has reached the shelter. This suggests that not only do inhibitory cells control escape initiation, but they also look to be important for telling the animal to stop when they reach safety,” explained Professor Branco.
To test this further, the team used a technique called optogenetics to directly manipulate the activity of neurons by exciting or inhibiting them. When they artificially increased the activity of the PAG inhibitory neurons, they found that escape probability decreased. When they inhibited the PAG inhibitory neurons, then escape probability increased. This confirmed that the PAG inhibitory neurons are acting as dial that can be turned up and down to control how sensitive the animal is to threat.
“To check whether these neurons are also important for controlling when escape stops, we first activated the neurons after the animals had started escaping and found that they stop before they reach the shelter. Then when we inhibited the neurons, we found that mice run past the shelter and do not stop escaping. This means the neurons have access to the information that the animal uses to know when it has reached safety,” explained Professor Branco.
The next step for the team is to understand how the experience of threat makes the system more or less excitable through the recruitment of these neurons. “If we were able to reveal the specific molecular pathway that links experience to the recruitment of these neurons, then it is conceivable that drugs could be developed to target this pathway so that the sensitivity could be dialled up or down in people with anxiety and PTSD,” concluded Professor Branco.
This research was funded by a Wellcome Senior Research Fellowship (214352/Z/18/Z), by the Sainsbury Wellcome Centre Core Grant from the Gatsby Charitable Foundation and Wellcome (GAT3755 and 219627/Z/19/Z) and by a European Research Council grant (Consolidator no. 864912), German Research Foundation postdoctoral fellowships (project no. 515465001; project no. STE 2605/1), the UCL Wellcome 4-year PhD Programme in Neuroscience, the SWC PhD Programme and the Max Planck Society.