The National Academies said the condition could involve up to 200 symptoms, make it difficult for people to work and last for months or years.One of the nation’s premier medical advisory organizations has weighed in on long Covid with a 265-page report that recognizes the seriousness and persistence of the condition for millions of Americans.More than four years since the start of the coronavirus pandemic, long Covid continues to damage many people’s ability to function, according to the National Academies of Sciences, Engineering and Medicine, a nongovernmental institution that advises federal agencies on science and medicine.“Long Covid can impact people across the life span, from children to older adults, as well as across sex, gender, racial, ethnic and other demographic groups,” it said, concluding that “long Covid is associated with a wide range of new or worsening health conditions and encompasses more than 200 symptoms involving nearly every organ system.”Here are some of the National Academies’ findings, drafted by a committee of 14 doctors and researchers:How many people have long Covid?The report cited data from 2022 suggesting that nearly 18 million adults and nearly a million children in the United States have had long Covid at some point. At the time of that survey, about 8.9 million adults and 362,000 children had the condition.Surveys showed that the prevalence of long Covid decreased in 2023 but, for unclear reasons, has risen this year. As of January, data showed nearly 7 percent of adults in the United States had long Covid.Diagnosis and consequencesThere is still no standardized way to diagnose the condition and no definitive treatments to cure it. “There is no one-size-fits-all approach to rehabilitation, and each individual will need a program tailored to their complex needs,” the National Academies said, advising that doctors should not require patients to have a positive coronavirus test to be diagnosed with long Covid.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.

24 minutes agoJames Gallagher

According to preliminary data from a multi-institution Phase III trial led by researchers at The University of Texas MD Anderson Cancer Center, intensity modulated proton therapy (IMPT) achieved similar clinical outcomes and offered significant patient benefits when compared to traditional intensity modulated radiation therapy (IMRT) as part of chemoradiation treatment for patients with oropharyngeal (head and neck) cancer.
The results were presented today at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting by Steven Frank, M.D., professor of Radiation Oncology and executive director of the Particle Therapy Institute at The University of Texas MD Anderson Cancer Center.
With a median follow-up of three years, the progression-free survival (PFS) rate was 83% and 83.5% for IMPT and IMRT, respectively, and IMPT was statistically non-inferior to IMRT. There was a significant reduction of malnutrition with IMPT, with 24% of patients sustaining their nutrition with less than 5% weight loss during treatment compared with 14% of those receiving IMRT. Additionally, there was a significant reduction of feeding-tube dependence with IMPT at 28%, compared to 42% with IMRT.
“The results of this multi-center Phase III randomized trial provide evidence for IMPT as a new standard-of-care treatment approach for the management of head and neck tumors,” Frank said. “This is significant for patients as it represents a curative, de-intensified option compared to traditional radiation therapy.”
Proton therapy has both biological and physical advantages over traditional radiation therapy using photons. Unlike photons, protons have mass and can be stopped by the human body. This allows proton radiation to be delivered specifically to the targeted area, limiting the amount that reaches nearby normal tissues. This trial represents the largest randomized Phase III trial to date to investigate proton therapy in comparison to traditional radiation.
The trial enrolled 440 patients at 21 sites in the U.S., with 219 receiving IMRT and 221 receiving IMPT. Patients were stratified based on human papillomavirus (HPV) status, smoking status and whether they had received induction chemotherapy. The primary endpoint of the study was the PFS rate at three years.
“Historically, these kind of large-scale trials to confirm the benefits of proton therapy have been challenging, due in part to relatively few patients having access to proton therapy centers,” Frank said.” Encouraging results like these demonstrate the benefits of proton therapy and hopefully help pave the way for increased access for patients in need.”
This study was funded by grants from the National Institutes of Health (NIH)/National Cancer Institute (NCI) (U19CA021239, R03CA188162, R56DE025248) and Hitachi. Frank reports proton-related grant funding by Hitachi and honoraria fees from Ion Beam Applications S.A. (IBA). He also has non-proton related health care relationships with Boston Scientific (consulting fees), Affirmed Pharma (NIH grant), and C4 Imaging (founder, scientific advisory committee, patents/royalties, ownership interest). 

A group of researchers at University of California San Diego has identified the cause of a “short-circuit” in cellular pathways, a discovery that sheds new light on the genesis of a number of human diseases.
The recent study, published in the journal Science Signaling, explores the biochemical mechanism that can interrupt the cellular communication chain — a disruptive interaction that Pradipta Ghosh, M.D., likens to a game-ending “buzzer.” Ghosh, a professor in the Departments of Medicine and Cellular and Molecular Medicine at University of California San Diego School of Medicine, and Irina Kufareva, Ph.D., an associate professor in the Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego, are the corresponding authors on the paper.
The paper explains the mechanism of “cross talk” between two cellular pathways, one initiated by proteins known as growth factors and by their cellular receptors. The second pathway is mediated by a completely different G protein-coupled set of cellular receptors (GPCRs). Both classes of receptors deliver molecular messages from outside to inside the cell and signal cells to change in some way. Kufareva says that members of the GPCR family are targets of around 34 percent of all the drugs approved by the U.S. Food and Drug Administration.
“GPCRs are important drug targets mainly due to their involvement in signaling pathways related to many diseases,” she explained, citing mental and endocrinological disorders, viral infections, cardiovascular and inflammatory conditions, and even cancer.
Growth factors enable a second, equally important communication pathway inside the cell that makes the cells grow and divide. Whereas GPCRs act through intracellular molecular switches (G proteins), growth factor receptors are conventionally thought to bypass the switches. However, Ghosh and Kufareva note that researchers had been suspicious about some kind of a potential conflict between the two pathways, and careful research allowed the UC San Diego team to identify it.
Ghosh said the conflict stems from problematic phosphorylation, the attachment of a phosphate group to the G protein molecule. She explained that the team used advanced mass spectrometry techniques to map all occurrences of phosphoevents, the sites on G proteins that were phosphorylated when cells were stimulated by growth factors. Then they checked how this changed the ability of G proteins to perform their normal job downstream of GPCRs.
“Whatever aspect of GPCR signaling we looked at, it was negatively impacted by almost all phosphoevents on the ‘switch’ protein — the G protein — that would be introduced by growth factors,” Kufareva said. “That was understandable when we looked at how these phosphoevents distorted the G protein structure. Growth factors effectively ‘steal’ G proteins from GPCRs and in this way paralyze their signaling.”
Further testing of the phosphoevents showed that one single amino acid was responsible for the G protein theft. Ghosh said the amino acid known as tyrosine is located at position 320 within the G protein, which happens to be on the side of the G protein that makes contact with G protein-coupled receptors.

“This specific tyrosine was identified almost a decade ago as a special ‘trigger point’ for G protein-coupled receptors to relay their signals. We began to think about the importance of such a coincidence,” Ghosh explained. “That’s when a light bulb went off in our heads: If cell communication were a game, the tyrosine at position 320 on the G protein would be the buzzer. If the growth factors got to it first and phosphorylated that site, the G protein-coupled receptors simply had no shot!”
Kufareva and Ghosh say that the group’s discovery has implications for the development of new therapies for a number of conditions, including cancer. Ghosh said that many pharmaceuticals on the market are effective in treating a wide range of diseases because the drugs target G protein-coupled receptors. But there remain a number of conditions without good drug therapies — fibrosis, chronic inflammation and cancers — because until now the interaction of these two pathways has not been understood.
“We believe our findings are likely to be both important and timely, and will contribute to other emerging studies mapping the landscape of these two major signaling pathways that control practically every process in our cells,” Ghosh said.
“Our work is especially relevant in that growth factors, their receptors, and G-protein-coupled receptors appear to be highly co-expressed in many cancers,” added Kufareva.
All authors on the paper are associated with UC San Diego. Suchismita Roy, Saptarshi Sinha and Ananta James Silas are members of the School of Medicine’s Department of Cellular and Molecular Medicine, while Majid Ghassemian is a member of the Department of Chemistry and Biochemistry, Biomolecular and Proteomics Mass Spectrometry Facility.
This paper was supported by the National Institutes of Health (CA238042, AI141630, CA100768 and CA160911 to Pradipta Ghosh; R21 AI149369, R01 GM136202, R21 AI156662, and R01 AI161880 to Irina Kufareva). Saptarshi Sinha was supported through the American Association of Immunologists Intersect Fellowship Program for Computational Scientist and Immunobiologists.

The length of telomeres that protect the ends of our chromosomes should be tightly regulated. Those that are too long predispose to cancer, and those that are too short lose their protective ability, resulting in telomere disorders with serious health consequences. Our cells prevent this excessive shortening by adding telomeric DNA to the ends of chromosomes. Researchers at Rockefeller recently showed that this process is mediated by two enzymes: telomerase and the CST-Polα/primase complex. Having determined how telomerase is recruited, scientists were left with a fundamental question: how does CST-Polα/primase find its way to the telomere?
Now, a new study published in Cell demonstrates that CST is recruited to the end of the telomere and regulated by subtle chemical changes made to POT1, a protein in the shelterin complex involved in telomere maintenance and implicated in cancer risk. The findings provide new insight into how human telomeres function at the molecular level, with implications for numerous diseases and disorders.
“After the discovery of telomerase, it took decades to figure out how it gets to the telomere. Now, just months after discovering that CST-Polα/primase is the second critical enzyme required for telomere maintenance, we understand the details of how it is recruited,” says Titia de Lange, the Leon Hess professor. “Moreover, we’ve found out how this process is regulated.”
Recruiting and regulating CST
Telomeres have two different types of strands, G-rich and C-rich. Scientists have long known how telomerase maintains the length of the G-rich strand, but only recently was it recognized that the same problem also exists for the C-rich strand. A recent study from the de Lange lab identified the CST-Polα/primase complex as the key regulator responsible for keeping that strand intact.
What remained to be seen was how CST, and its associated enzyme Polα-primase, travels to telomere to facilitate C-strand maintenance across replication cycles. Sarah Cai, a PhD candidate at Rockefeller, began investigating this piece of the telomere puzzle. Building on a decade of the de Lange lab’s groundwork on CST, Cai added cryo-EM to the techniques used in this study while being co-advised by Rockefeller’s Thomas Walz.
“The interdisciplinary nature of the study is one of the most exciting parts,” Cai says. “It was a very successful double-lab effort, making use of many different technologies.” Walz, whose research focuses on cryo-EM, noted how Cai incorporated AlphaFold, a deep-learning algorithm that can predict the unique 3D structures of proteins, into her work.

With the combined power of biochemistry, structural biology, and cell biology, the team ultimately confirmed that CST is recruited to telomeres by the POT1 protein. Once CST-Polα/primase is onsite, the addition and removal of phosphate groups from POT1 appears to function as an on/off switch that coordinates the final steps of telomere replication. Phosphorylated POT1 ensures that CST-Polα/primase remains inactive until telomerase has finished its job, upon which the dephosphorylation of POT1 activates CST-Polα/primase to add the finishing touches to the telomere.
Telomere disorders and cancer
Next, the team will look for specific enzymes that attach and remove phosphates during this process, controlling the on/off switch on POT1, and determining their role in regulating CST-Polα/primase recruitment and activity. A better understanding of how CST is recruited to the telomere cannot come fast enough for patients suffering from telomere disorders, such as Coats plus syndrome, a severe multi-organ disease characterized by abnormalities in the eyes, brain, bones, and GI tract.
“For a long time, we didn’t know why mild alterations in single amino acids would cause such a devastating disease,” Cai says. “We now have a better idea of how these mutations affect the recruitment of this critical telomere maintenance machine and lead to Coats plus syndrome.”
The findings will also impact their cancer research. The de Lange lab has spent decades studying how telomere shortening contributes to tumor suppression and genome instability in cancer, and the present research may ultimately help answer questions that lie at the heart of tumor development.
“Anything critical to telomere length regulation may well be critical to cancer prevention too,” de Lange says. “This is a major focus of our lab, and one of the reasons we’ll be looking into the interplay between CST-Polα/primase and telomerase more closely in the future.”

Adolescents with an internet addiction undergo changes in the brain that could lead to additional addictive behaviour and tendencies, finds a new study by UCL researchers.
The findings, published in PLOS Mental Health, reviewed 12 articles involving 237 young people aged 10-19 with a formal diagnosis of internet addiction between 2013 and 2023.
Internet addiction has been defined as a person’s inability to resist the urge to use the internet, negatively impacting their psychological wellbeing, as well as their social, academic and professional lives.
The studies used functional magnetic resonance imaging (fMRI) to inspect the functional connectivity (how regions of the brain interact with each other) of participants with internet addiction, both while resting and completing a task.
The effects of internet addiction were seen throughout multiple neural networks in the brains of adolescents. There was a mixture of increased and decreased activity in the parts of the brain that are activated when resting (the default mode network).
Meanwhile, there was an overall decrease in the functional connectivity in the parts of the brain involved in active thinking (the executive control network).
These changes were found to lead to addictive behaviours and tendencies in adolescents, as well as behaviour changes associated with intellectual ability, physical coordination, mental health and development.

Lead author, MSc student, Max Chang (UCL Great Ormond Street Institute for Child Health) said: “Adolescence is a crucial developmental stage during which people go through significant changes in their biology, cognition, and personalities. As a result, the brain is particularly vulnerable to internet addiction related urges during this time, such as compulsive internet usage, cravings towards usage of the mouse or keyboard and consuming media.
“The findings from our study show that this can lead to potentially negative behavioural and developmental changes that could impact the lives of adolescents. For example, they may struggle to maintain relationships and social activities, lie about online activity and experience irregular eating and disrupted sleep.”
With smartphones and laptops being ever more accessible, internet addiction is a growing problem across the globe. Previous research has shown that people in the UK spend over 24 hours every week online and, of those surveyed, more than half self-reported being addicted to the internet.
Meanwhile, Ofcom found that of the 50 million internet users in the UK, over 60% said their internet usage had a negative effect on their lives — such as being late or neglecting chores.
Senior author, Irene Lee (UCL Great Ormond Street Institute of Child Health), said: “There is no doubt that the internet has certain advantages. However, when it begins to affect our day-to-day lives, it is a problem.
“We would advise that young people enforce sensible time limits for their daily internet usage and ensure that they are aware of the psychological and social implications of spending too much time online.”
Mr Chang added: “We hope our findings will demonstrate how internet addiction alters the connection between the brain networks in adolescence, allowing physicians to screen and treat the onset of internet addiction more effectively.

“Clinicians could potentially prescribe treatment to aim at certain brain regions or suggest psychotherapy or family therapy targeting key symptoms of internet addiction.
“Importantly, parental education on internet addiction is another possible avenue of prevention from a public health standpoint. Parents who are aware of the early signs and onset of internet addiction will more effectively handle screen time, impulsivity, and minimise the risk factors surrounding internet addiction.”
Study limitations
Research into the use of fMRI scans to investigate internet addiction is currently limited and the studies had small adolescent samples. They were also primarily from Asian countries. Future research studies should compare results from Western samples to provide more insight on therapeutic intervention.

A team of UC Davis Health researchers discovered that a common anti-inflammatory drug, mesalamine, can replace the work of good bacteria in fighting the nasty fungus Candida albicans in the gut.
C. albicans, or candida, is known to cause yeast infections. In some cases, it develops into invasive candidiasis, a potentially fatal infection occurring mostly in patients with compromised immunity.
The researchers found that this fungus can’t grow without an oxygen supply. Their study in mice showed that the drug can maintain a low oxygen (hypoxia) environment that prevents fungal bloom in the gut.
Their study appears today in Cell Host & Microbe.
Antibiotic use may lead to fungal bloom in the gut
The team studied how C. albicans colonizes the gut. The fungus, best known for causing vaginal yeast infections, is usually treated with a topical or oral antifungal without serious side effects. It also harmlessly lives in the gut of around 60% of people.
Yet, when the body’s immunity goes down due to cancer or chemotherapy, the fungus may grow beyond the colon and spread throughout the body. In such cases, the patient develops invasive candidiasis.

“Invasive candidiasis is a potentially deadly infection with a mortality rate of around 50%. That’s even with the best available treatment,” explained the study’s lead author Andreas Bäumler. Bäumler is a distinguished professor in the Department of Medical Microbiology and Immunology.
Patients with leukemia and other blood cancers may need to take antibiotics. This use may cause an imbalance in the gut’s microbial community. It reduces Clostridia, a group of bacteria that promotes resistance to fungi colonization in the gut. With less Clostridia, C. albicans grows and colonizes in the tract.
“A bloom of C. albicansin the gut during antibiotic therapy is the most common cause of candidemia in people treated for blood cancers,” Bäumler explained. Candidemia is the presence of fungi or yeast in the blood.
Bäumler and his team wanted to understand the factors involved in antibiotic-induced colonization of C. albicans in the gut.
Candida loves simple sugars and oxygen
They first colonized germ-free mice with Candida to see what the fungus consumed to bloom. They realized that Candida really liked simple sugars, similar to those found in high-sugar diets. Then, they tested its growth in a petri dish. They placed Candida with simple sugars in an aerobic (with oxygen) setting, and the fungi bloomed.

“A healthy gut has low oxygen. So, we repeated the test in a hypoxia setting,” Bäumler said. The fungi didn’t grow despite the presence of sugars. This meant oxygen is a necessary condition for Candida growth.
The role of probiotics in preventing fungal growth
The team did a series of experiments that showed antibiotic use reduced Clostridiain the gut. Giving mice probiotics, such as Clostridia, prevented C. albicans from growing in the gut. Yet, probiotics can be killed by antibiotics and cancer therapy. For this reason, probiotics would not help patients with leukemia or other blood cancers.
“Probiotics are often not safe in patients at the highest risk for invasive candidiasis,” Bäumler said. “Finding a therapy that can function like probiotics but can endure the impact of cancer treatment and antibiotics was important.”
Anti-inflammatory drugs as faux-biotics
The team explored 5-aminosalicylic acid (5-ASA) as a safer way to control C. albicansin the gut. 5-ASA, also known as mesalamine, is an anti-inflammatory drug. It is used to treat inflammatory bowel diseases (IBD) like Crohn’s disease and ulcerative colitis.
The team tested 5-ASA in mice treated with antibiotics. They found that the drug could replace the work of probiotics by preventing oxygen in the colon and C. albicans from expanding in the gut.
“Limiting oxygen in the gut by replacing the function of good bacteria could be a strategy for reducing invasive candidiasis,” Bäumler said. “Our study opens a totally new treatment option for fatal fungal infections, especially for patients with cancer. After all, fungi cannot become resistant against hypoxia.”
The team proposed the term “faux-biotics” to refer to products, such as 5-ASA, that mimic the function of probiotics like Clostridia.
The first coauthors of the study are Hannah Savage, Derek Bays and Connor Tiffany. The other co-authors are Mariela Gonzalez, Eli Bejarano, Thaynara Carvalho, Zheng Luo, Hugo Masson, Henry Nguyen, Renato Santos, Krystle Reagan and George Thompson of UC Davis.

An independent group of experts expressed concerns that the data from clinical trials did not outweigh risks for treatment of post-traumatic stress disorder.An independent advisory panel of the Food and Drug Administration rejected the use of MDMA-assisted therapy for post-traumatic stress disorder on Tuesday, highlighting the unparalleled regulatory challenges of a novel therapy using an illegal drug commonly known as Ecstasy.Before the vote, members of the panel raised concerns about the designs of the two studies submitted by the drug’s sponsor, Lykos Therapeutics. Many questions focused on the fact that study participants were by and large able to correctly guess whether they had been given MDMA, also known by the names of Ecstasy or molly. The panel voted 9-2 on whether the MDMA-assisted therapy was effective, and voted 10-1 on whether the proposed treatment’s benefits outweighed its risks.Other panelists expressed concerns over the drug’s potential cardiovascular effects, and possible bias among the therapists and facilitators who guided the sessions and may have positively influenced patient outcomes. A case of misconduct involving a patient and therapist in the study also weighed on some panelists’ minds.Many of the committee members said they were especially worried about the failure of Lykos to collect detailed data from participants on the potential for abuse of a drug that generates feelings of bliss and well-being.“I absolutely agree that we need new and better treatments for PTSD,” said Paul Holtzheimer, deputy director for research at the National Center for PTSD, a panelist who voted no on the question of whether the benefits of MDMA-therapy outweigh the risks.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.

2 days agogettyMajor hospitals in London have declared a critical incident after a cyber-attack led to operations being cancelled and emergency patients being diverted elsewhere.

The organ, from a genetically modified animal, failed because of a lack of blood flow, surgeons said, but did not appear to have been rejected by the body.Surgeons removed the kidney of a genetically engineered pig from a critically ill patient last week after the organ was damaged by inadequate blood flow related to a heart pump that the woman had also received, according to officials at NYU Langone Transplant Institute.The patient, Lisa Pisano, 54, who is still hospitalized, went back on kidney dialysis after the pig’s organ was removed. She lived with the transplanted organ for 47 days, Dr. Robert Montgomery, director of the institute, said. The kidney showed no signs of organ rejection.“Lisa is in stable condition, and her left ventricular assist device is still functioning,” Dr. Montgomery said, referring to the heart pump. “We are hoping to get Lisa back home to her family soon.”“Lisa is a pioneer and a hero in the effort to create a sustainable option for people waiting for an organ transplant,” he added. In April, Ms. Pisano became the second person to receive a kidney transplanted from a genetically modified pig. Hers was an especially complicated case: She has heart failure and kidney failure, and received the organ just eight days after receiving a mechanical heart pump. Ms. Pisano was at risk of dying without the heart pump, a device implanted in patients who need a heart transplant. But there is an acute shortage of human kidneys available from donors, and her heart disease made her ineligible to receive one.She is the first patient with a heart pump known to have received an organ transplant of any kind, NYU Langone Health officials said. Patients with kidney failure are usually ineligible to receive a heart pump because of the high risk of death.The first patient to receive a kidney from a genetically engineered pig was Richard Slayman, 62, who underwent the procedure in March at Mass General Brigham in Boston.He was well enough to go home from the hospital two weeks after the surgery, but he suffered from complex medical problems and died within two months.Great strides have been made in recent years in the transplantation of organs from animals into humans following such technological innovations as cloning and gene-editing.The procedures are still experimental, however, and so far only patients who are so sick that they are not eligible for a human organ and may die without treatment have been cleared to receive animal organs.The two transplants of pig kidneys this year were approved under the Food and Drug Administration’s compassionate use, or expanded access, program for patients with life-threatening conditions.