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A team of Massachusetts General Hospital (MGH) researchers has discovered how an important class of anti-cancer drugs called PARP inhibitors works, a finding that could help improve treatment and prolong survival for patients with breast cancer and other malignancies.
PARP (poly[ADP-ribose] polymerase) inhibitors such as olaparib (Lynparza), rucaparib (Rubraca) and niraparib (Zejula) are used to treat patients with cancers of the breast, ovaries, prostate and pancreas, and are particularly effective against tumors carrying mutations in the BRCA1 and BRCA2 tumor suppressor genes.
PARP inhibitors, like many other classes of anti-cancer drugs, are known to work by interfering with the ability of cancer cells to repair themselves after experiencing damage to their DNA, but exactly how PARP inhibitors selectively kill cancer cells was poorly understood.
But as Zou Lee, PhD, and colleagues found, PARP inhibitors work by creating gaps in tumor-cell DNA that remain present through multiple cell cycles (the process by which cells replicate: grow, divide, repeat). They also found that BRCA1/2 mutant cancer cells cannot respond to these gaps and therefore fail to repair properly, leading to the death of tumor cells.
“These findings provide a mechanistic explanation of the selectivity of PARP inhibitors toward cancer cells, and they also offer new opportunities to improve the use of PARP inhibitors in the clinic,” says Zou, scientific co-director of the Mass General Cancer Center and the Center for Cancer Research, and professor of Pathology at Harvard Medical School.
“This work finally explains why PARP inhibitors kill BRCA-mutant cells selectively,” he adds.

Hypertrophic cardiomyopathy (HCM) is the most common of all genetic heart diseases and is the leading cause of sudden cardiac death. It is characterized by an abnormal thickening of the heart muscle, which over time can lead to cardiac dysfunction and, ultimately, heart failure.
A paper published in the Proceedings of the National Academy of Sciences (PNAS) and co-authored by Beth Pruitt, a UC Santa Barbara professor of mechanical engineering and the director of the campus’s Institute for BioEngineering, describes the results of a complex long-term collaboration that included researchers at Stanford University, the University of Washington, and the University of Kentucky. The study has led to new understanding of how genetic mutations play out at the cellular level to cause HCM, and new perspectives on how to prevent it.
In their paper, the authors explain that more than one thousand genetic mutations that cause HCM have been identified. The majority of them are found in genes that encode sarcomeric proteins, the structural building blocks of heart muscle responsible for generating and regulating contraction and relaxation. Roughly a third of the mutations are located in beta cardiac myosin, the primary protein that drives contraction of the heart cells. Contraction of the heart muscle, and every other muscle in our bodies, results from a process in which the motor protein myosin “walks” along a chain of actin molecules, a process known as the cross-bridge cycle. During this process, chemical energy in the form of ATP is converted to mechanical energy, ultimately leading to cardiac contraction.
Prior to a contraction, the head of one strand of an intertwined two-strand myosin molecule is tucked up against an actin molecule. Muscle contraction is initiated when a molecule of ATP, known as the “energy currency” of biological systems, binds to the myosin head. The myosin head, and the attached ATP, then detaches from the actin, initiating hydrolysis of the ATP, which is transformed into ADP plus a phosphate group. That process releases energy that “cocks” the myosin protein into a high-energy state and changes the shape of the myosin so that it is ready to crawl along the actin. At that point, the phosphate is released from the myosin, causing the myosin to push on the actin and release the phosphate, which leads the myosin to walk to the next chain of actin and contract the muscle. All of this, involving millions of heads of myosin walking across actin in steps that take microseconds to complete, must occur at the proper rate in order to maintain heart health.
Because HCM is often observed in patients having mutations in the beta cardiac myosin protein, it had been hypothesized that HCM mutations cause a cascade of events that manifest, ultimately, in damage to the heart itself. This study put that idea to the test, focusing on a single mutation, P710R, which dramatically decreased in vitro motility velocity — the rate at which the myosin motor walks on actin — in contrast to other MYH7 mutations, which led to increased motility velocity.
The overarching research question of this project was to learn how a mutation linked to heart disease in patients changes heart function at a cellular level.

We asked experts to describe the most prevalent symptoms they’re seeing right now among people with Covid-19.Two years ago, a sneeze or a cough wouldn’t have been cause for concern, but now even the mildest of symptoms can leave us wondering, “Do I have Covid?”Early in the pandemic, we learned about the hallmark signs of infection, which can include loss of taste and smell, fever, cough, shortness of breath and fatigue. But what about now, more than a year later? Have symptoms changed given that the Delta variant is currently the most common form of the virus in the United States?There is little data on this question and much left to untangle.Unvaccinated patients make up the vast majority of those hospitalized with Covid-19, so they may be more likely to develop severe symptoms, like trouble breathing, or persistent pain or pressure in the chest. In areas with lower vaccination rates, like Louisiana, Texas and Arkansas, unvaccinated children and young adults are being sent to the hospital in larger numbers than they were at other points during the pandemic. Researchers do not yet know for sure whether Delta alone is responsible for these severe symptoms or if it is the surge in childhood infections, which can result in more hospitalizations. The Delta variant is nearly twice as contagious as prior variants and just as contagious as chickenpox. It replicates rapidly in the body, and people carry large amounts of the virus in their nose and throat.Dr. Andrew T. Chan, an epidemiologist and physician at Massachusetts General Hospital and one of the lead investigators of the Covid Symptom Study, has been tracking millions of people from Britain, the United States and Sweden via an app that asks participants to monitor their symptoms. A preprint using data from the study that has not yet been published in a peer-reviewed journal, suggests that those who are vaccinated are well protected against Delta. Breakthrough infections, while rare, tend to produce milder symptoms that are of shorter duration.At this point, nearly 90 percent of the adult population in Britain has received at least one dose of the vaccine. In the United States, 71 percent of adults are partially vaccinated.Among vaccinated adults, “the symptoms we are seeing now are much more commonly identified with the common cold,” Dr. Chan said. “We are still seeing people presenting with a cough, but we are also seeing a higher prevalence of things like runny nose and sneezing.” Headaches and sore throat are other top complaints, he added. Fever and loss of taste and smell are being reported to a lesser degree.Dr. Chan said the researchers started to see milder reported symptoms around the time the Delta variant became prevalent in Britain, starting in the late spring, which also coincided with the country’s mass vaccination program.Pediatricians in New York City, where 67 percent of adults are fully vaccinated, say they are seeing many of the same symptoms in children that they have seen since the start of the pandemic, and that the more severe cases tend to be among unvaccinated adolescents, especially those with underlying conditions like diabetes or obesity. Some toddlers or school-age children can get very ill from Covid too, but doctors don’t always know why one kid gets much sicker than another, said Dr. Sallie Permar, pediatrician-in-chief at NewYork-Presbyterian and Weill Cornell Medicine.Fever, cough, fatigue, headache and sore throat are the “classic presentation of Covid” among symptomatic children, she added.If your child has any potential Covid symptoms, including gastrointestinal problems, arrange for both yourself and your child to get a Covid test and then stay home until the results are negative, said Dr. Adam Ratner, director of the division of pediatric infectious diseases at Hassenfeld Children’s Hospital at N.Y.U. Langone.“That’s part of how we keep schools safe,” he added.Testing is essential for adults too, the experts said. Even if you have been vaccinated and your symptoms are mild, it’s best to get tested. The Centers for Disease Control and Prevention believes that vaccinated people can still transmit the virus to others.“It’s a time to be humble about the fact that this is a new variant. We’re still learning,” said Dr. Mark Mulligan, the director of the N.Y.U. Langone Vaccine Center and the chief of infectious diseases at N.Y.U. Langone Health. “Be cautious and err on the side of caution in terms of going ahead and getting a test.”

A new strategy for modeling the spread of COVID-19 incorporates smartphone-captured data on people’s movements and shows promise for aiding development of optimal lockdown policies. Ritabrata Dutta of Warwick University, U.K., and colleagues present these findings in the open-access journal PLOS Computational Biology.
Evidence shows that lockdowns are effective in mitigating the spread of COVID-19. However, they do come at a high economic cost, and in practice, not everybody follows government guidance on lockdowns. Thus, Dutta and colleagues propose, an optimal lockdown strategy would balance between controlling the ongoing COVID-19 pandemic and minimizing the economic costs of lockdowns.
To help guide such a strategy, the researchers developed new mathematical models that simulate the spread of COVID-19. The models focus on England and France and — using a statistical approach known as approximate Bayesian computation — they incorporate both public health data and data on changes in people’s movements, as captured by Google via Android devices; this mobility data serves as a measure of the effectiveness of lockdown policies.
Then, the researchers demonstrated how their models could be applied to design optimal lockdown strategies for England and France using a mathematical technique called optimal control. They showed that it is possible to design effective lockdown protocols that allow partial reopening of workplaces and schools, while taking into account both public health costs and economic costs. The models can be updated in real time, and they can be adapted to any country for which reliable public health and Google mobility data are available.
“Our work opens the door to a larger integration between epidemiological models and real-world data to, through the use of supercomputers, determine best public policies to mitigate the effects of a pandemic,” Dutta says. “In a not-so-distant future, policy makers may be able to express certain prioritization criteria, and a computational engine, with an extensive use of different datasets, could determine the best course of action.”
Next, the researchers plan to refine their country-wide models to work at smaller scales; specifically, each of the 348 local district authorities of the U.K.
The researchers add, “The integration of big data, epidemiological models and supercomputers can help us design an optimal lockdown strategy in real time, while balancing both public health and economic costs.”
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A high-fat diet disrupts the biology of the gut’s inner lining and its microbial communities — and promotes the production of a metabolite that may contribute to heart disease, according to a study published Aug. 13 in the journal Science.
The discoveries in animal models support a key role for the intestines and microbiota in the development of cardiovascular disease, said Mariana Byndloss, DVM, PhD, assistant professor of Pathology, Microbiology and Immunology at Vanderbilt University Medical Center.
The intestines, she noted, have been relatively understudied by scientists seeking to understand the impact of obesity.
“Before COVID, obesity and metabolic syndrome were considered the pandemic of the 21st century. Right now, roughly 40% of the U.S. population is obese, and that percentage is predicted to climb,” Byndloss said. “Our research has revealed a previously unexplored mechanism for how diet and obesity can increase risk of cardiovascular disease — by affecting the relationship between our intestines and the microbes that live in our gut.”
In previous studies, Byndloss and Andreas Bäumler, PhD, at the University of California at Davis, found that the epithelial cells lining the intestines and gut microbes share a mutually beneficial relationship that promotes a healthy gut environment. They wondered if diseases like obesity affect this relationship.
The collaborating research teams found that a high-fat diet causes inflammation and damages intestinal epithelial cells in animal models. The high-fat diet impairs the function of energy-generating mitochondria, Byndloss explained, causing the intestinal cells to produce more oxygen and nitrate.

Abnormal cells that go on develop into oesophageal cancer – cancer that affects the tube connecting the mouth and stomach – start life as cells of the stomach, according to scientists at the University of Cambridge.
The study, published today in Science, found that a particular subtype of oesophageal cancer known as oesophageal adenocarcinoma is always preceded by Barrett’s oesophagus – abnormal cells of the oesophagus – even if these cells are no longer visible at the time of cancer diagnosis. This confirms that screening for Barrett’s is an important approach to oesophageal cancer control.
Cancer of the oesophagus is the sixth most deadly cancer, and oesophageal adenocarcinoma is on the rise in western countries. Scientists and doctors have known for some time that the development of this cancer is linked with Barrett’s oesophagus, which shows up in endoscopy as a pink ‘patch’ in the surface of oesophagus and affects around one out of every 100 to 200 people in the United Kingdom – and between 3 and 13 people out of 100 with this condition will go on to develop oesophageal adenocarcinoma in their lifetime. However, the question of where these abnormal cells come from has been a mystery that has baffled scientists for decades.
A multidisciplinary group of scientists led by Professor Rebecca Fitzgerald at the Medical Research Council Cancer Unit, University of Cambridge, today provides the most comprehensive explanation to date.
Dr Lizhe Zhuang, joint first author of the study, said: “It’s intriguing that, although Barrett’s oesophagus predominately occurs in the lower part of oesophagus close to stomach, it has so-called ‘goblet cells’ resembling a much more distant organ, the small intestine. Over the past twenty years there have been at least six different hypotheses about the origin of Barrett’s oesophagus. Using the latest techniques, we believe we have arrived at an answer to this mystery.”
The research team analysed tissue samples from patients with Barrett’s oesophagus and from organ donors who have never had the condition. The samples were collected as part of the Cambridge Biorepository for Translational Medicine at Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation Trust.

Most of us remember a time when we could eat anything we wanted and not gain weight. But a new study suggests your metabolism, the rate at which you burn calories, actually peaks much earlier and starts its inevitable decline later than you might think.
The findings appear in the journal Science.
“As we age, there are a lot of physiological changes that occur in the phases of our life such as during puberty and in menopause. . What’s odd is that the timing of our ‘metabolic life stages’ doesn’t appear to match the markers we associate with growing up and getting older,” said study co-author Jennifer Rood, PhD, Associate Executive Director for Cores and Resources at Pennington Biomedical Research Center.
Four Pennington Biomedical researchers were part of an international team of scientists who analyzed the average calories burned by more than 6,600 people as they went about their daily lives. The participants’ ages ranged from one week old to 95 years, and they lived in 29 different countries. The other Pennington Biomedical scientists are Peter Katzmarzyk, PhD, Associate Executive Director for Population and Public Health Sciences; Corby Martin, PhD, Professor and Director, Ingestive Behavior Laboratory; and Eric Ravussin, PhD, Associate Executive Director for Clinical Science.
Most previous large-scale studies measured how much energy the body uses for basic vital functions — breathing, digesting, and pumping blood — the calories you need just to stay alive. But basic functions account for just 50 percent to 70 percent of the calories we burn each day. They don’t include the energy we spend doing everything else: washing the dishes, walking the dog, breaking a sweat at the gym, even just thinking or fidgeting.
To come up with a number for total daily energy expenditure, the researchers turned to the “doubly labeled water” method. It’s a urine test that involves having a person drink water in which the hydrogen and oxygen in the water molecules have been replaced with naturally occurring “heavy” forms, and then measures how quickly they’re flushed out.

Jazz Pharmaceuticals brought in more than $1.7 billion last year selling GHB to narcolepsy patients. With the new approval, sales could soar.In the 1960s, the drug was given to women during childbirth to dampen their consciousness. In the 1990s, an illicit version made headlines as a “date rape” drug, linked to dozens of deaths and sexual assaults.And for the last two decades, a pharmaceutical-grade slurry of gamma-hydroxybutyrate, or GHB, has been tightly regulated as a treatment for narcolepsy, a disorder known for its sudden sleep attacks.Now, the Food and Drug Administration has approved the drug for a new use: treating “idiopathic hypersomnia,” a mysterious condition in which people sleep nine or more hours a day, yet never feel rested. Branded as Xywav, the medication is thought to work by giving some patients restorative sleep at night, allowing their brains to be more alert when they wake up. It is the first approved treatment for the illness.But some experts say the publicly available evidence to support the new approval is weak. And they worry about the dangers of the medication, which acts so swiftly that its label advises users to take it while in bed. Xywav and an older, high-salt version called Xyrem have a host of serious side effects, including breathing problems, anxiety, depression, sleepwalking, hallucinations and suicidal thoughts.GHB “has serious safety concerns, both in terms of its abuse liability and its addictive potential,” said Dr. Lewis S. Nelson, the director of medical toxicology at Rutgers New Jersey Medical School.An estimated 40,000 people in the United States have been diagnosed with idiopathic hypersomnia, but Dr. Nelson said that many more people with daytime drowsiness might wind up with this diagnosis now that it has an F.D.A.-approved treatment. The disorder’s hallmark symptoms — sleep cravings, long naps and brain fog — overlap with many other conditions.The more people who take the drug, the more opportunity for abuse. “The potential for the scope of use to expand is very real,” Dr. Nelson said. “So that is concerning to me.”The new approval is a boon for Jazz Pharmaceuticals, based in Dublin, which brought in more than $1.7 billion last year selling Xyrem and Xywav to about 15,300 people, most with narcolepsy.“We’re really excited about bringing the benefit of this effective medication to more patients,” said Bruce Cozadd, the chairman and chief executive of Jazz, which announced the new approval on Thursday.On the black market, homemade GHB — also known as liquid ecstasy, goop and G — can be bought by the capful for $5 to $25. But nightly treatments of Xyrem and Xywav cost roughly $100,000 a year. The new approval will make it much easier for hypersomnia patients to get insurance coverage for Xywav.Many doctors and patients have never heard of idiopathic hypersomnia, Mr. Cozadd said, but Jazz will aim to change that. “There’s an educational effort that we’ll be part of,” he said, “which is really making sure there’s a better understanding among treaters and among patients of the condition and its treatment.”The F.D.A. did not immediately respond to a request for comment.In March, Jazz and the Hypersomnia Foundation, a patient advocacy group, began an awareness campaign — “I have IH” — which included an online survey of health care providers’ knowledge of the condition (it was low), and advertisements in Times Square.“I never thought I’d live to see that day — it was very emotional,” said Betsy Ashcraft, the treasurer of the foundation’s board of directors, whose adult son has idiopathic hypersomnia. (Jazz paid the foundation’s board members, who are volunteers, for their time consulting on the campaign, she said.)GHB is an old drug, first synthesized by a Russian chemist in 1874. A century later, it was sold as a dietary supplement in the United States, and academic researchers began reporting that it greatly improved the nighttime sleep of people with narcolepsy and curbed their daytime sleep attacks, called cataplexy.In 1994, the F.D.A. approached a Minnesota drug company called Orphan Medical to investigate GHB as a treatment for narcolepsy. The government gives incentives — including tax credits and seven years of market exclusivity — to develop drugs for diseases that have small patient markets.But at the same time, illicit GHB was becoming a big problem. At low doses, the odorless powder can trigger euphoria and sexual arousal, making it popular at parties and raves. At high doses, especially when mixed with other downers like alcohol, it can knock a person out without any memory of what happened.In 2000, after GHB had been linked to sexual assaults and deaths, Congress passed a law that made the drug illegal, but allowed for future medical uses. Later that year, Orphan Medical sought F.D.A. approval of Xyrem for narcolepsy..css-1xzcza9{list-style-type:disc;padding-inline-start:1em;}.css-rqynmc{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:0.9375rem;line-height:1.25rem;color:#333;margin-bottom:0.78125rem;}@media (min-width:740px){.css-rqynmc{font-size:1.0625rem;line-height:1.5rem;margin-bottom:0.9375rem;}}.css-rqynmc strong{font-weight:600;}.css-rqynmc em{font-style:italic;}.css-yoay6m{margin:0 auto 5px;font-family:nyt-franklin,helvetica,arial,sans-serif;font-weight:700;font-size:1.125rem;line-height:1.3125rem;color:#121212;}@media (min-width:740px){.css-yoay6m{font-size:1.25rem;line-height:1.4375rem;}}.css-1dg6kl4{margin-top:5px;margin-bottom:15px;}#masthead-bar-one{display:none;}#masthead-bar-one{display:none;}.css-1pxllx6 header h4{font-family:nyt-cheltenham,georgia,’times new roman’,times,serif;font-weight:500;font-size:1.25rem;line-height:1.5625rem;margin-bottom:5px;}@media (min-width:740px){.css-1pxllx6 header h4{font-size:1.5625rem;line-height:1.875rem;}}.css-1pd7fgo{background-color:white;border:1px solid #e2e2e2;width:calc(100% – 40px);max-width:600px;margin:1.5rem auto 1.9rem;padding:15px;box-sizing:border-box;}@media (min-width:740px){.css-1pd7fgo{padding:20px;width:100%;}}.css-1pd7fgo:focus{outline:1px solid #e2e2e2;}#NYT_BELOW_MAIN_CONTENT_REGION .css-1pd7fgo{border:none;padding:20px 0 0;border-top:1px solid #121212;}.css-1pd7fgo[data-truncated] .css-rdoyk0{-webkit-transform:rotate(0deg);-ms-transform:rotate(0deg);transform:rotate(0deg);}.css-1pd7fgo[data-truncated] .css-eb027h{max-height:300px;overflow:hidden;-webkit-transition:none;transition:none;}.css-1pd7fgo[data-truncated] .css-5gimkt:after{content:’See more’;}.css-1pd7fgo[data-truncated] .css-6mllg9{opacity:1;}.css-1rh1sk1{margin:0 auto;overflow:hidden;}.css-1rh1sk1 strong{font-weight:700;}.css-1rh1sk1 em{font-style:italic;}.css-1rh1sk1 a{color:#326891;-webkit-text-decoration:underline;text-decoration:underline;text-underline-offset:1px;-webkit-text-decoration-thickness:1px;text-decoration-thickness:1px;-webkit-text-decoration-color:#ccd9e3;text-decoration-color:#ccd9e3;}.css-1rh1sk1 a:visited{color:#333;-webkit-text-decoration-color:#ccc;text-decoration-color:#ccc;}.css-1rh1sk1 a:hover{-webkit-text-decoration:none;text-decoration:none;}A subsequent meeting of an F.D.A. advisory committee brought charged testimony both for and against the drug. A lawyer who had taken GHB for narcolepsy for 19 years testified that his cataplexy “disappeared almost overnight,” with no side effects. The next speaker described how her daughter had bought GHB as a supplement for bodybuilding and became addicted. “I am here today to tell you how GHB killed my daughter,” she said.The advisory committee recommended the agency approve Xyrem for narcolepsy with cataplexy, which it did in 2002. Three years later, Orphan was acquired by Jazz.Xyrem contains a lot of salt, increasing a user’s risk of hypertension. The low-sodium Xywav was approved for narcolepsy last year, and Jazz has been urging doctors — with much success — to switch patients to the new brand. As executives pointed out in a recent earnings call, the shift is good news for Jazz’s business: Xyrem will most likely begin to compete with generic versions of the drug next year, whereas Xywav will have market exclusivity until at least 2027.Both prescriptions are tightly controlled through a safety program (known as a REMS) in which a single pharmacy ships the drug and regularly monitors patients and their doctors. Through this strict program, Jazz receives regular reports about any negative drug experiences reported by patients, and must disclose such cases to the F.D.A.Xyrem, left, and Xywav, the low-sodium version of the drug.As of June 30, the F.D.A. had recorded more than 27,000 “serious adverse events” for patients taking Xyrem or Xywav, including 753 deaths, according to the agency’s public database of such reports. (The F.D.A. defines serious events as those that were life threatening or led to hospitalization, serious medical consequences or death. However, these reports could be inaccurate or incomplete, the agency notes. Some of the events happened to people taking multiple drugs, and no single report can prove a drug caused illness.)“For some years I’ve had questions about whether this drug has benefits that exceed its high risks,” said Thomas Moore, a researcher at the Center for Drug Safety and Effectiveness at Johns Hopkins University, who in 2014 published a report recommending that the F.D.A. re-evaluate Xyrem.“F.D.A. approval of Xywav is based on both its benefit and its risks,” said Mr. Cozadd of Jazz. “Clearly F.D.A. believes, as we do, that used properly the drug is very beneficial for these patients.”In the years after Xyrem was approved for narcolepsy, Jazz ran afoul of the federal government for inappropriately marketing the drug for unapproved conditions, including insomnia, depression and fibromyalgia, a chronic condition involving pain and fatigue that affects at least four million people in the United States. The transgression cost the company $20 million in fines.In 2010, Jazz tried to get the drug approved to treat fibromyalgia, but an F.D.A. advisory committee voted overwhelmingly against the idea.“The data to support its benefit was infinitesimally small,” said Dr. Nelson of Rutgers, who was on that panel. Given the large size of the fibromyalgia population, the committee deemed the risks too high, he said: “Even with REMS, it just seemed like a potentially catastrophic idea.”The F.D.A. granted the new approval for hypersomnia without asking an advisory panel to weigh in. Jazz’s application was based on a small clinical trial in which 115 patients were given Xywav for 12 to 16 weeks, leading to decreases in scores on a sleepiness scale. After that acclimation period, about half of the volunteers were switched to a placebo for two weeks, which led to marked increases in their sleepiness scores.“Those under placebo deteriorated very rapidly,” said Dr. Isabelle Arnulf, a sleep disorder specialist at the Pitié-Salpêtrière University Hospital in Paris, who has studied hypersomnia for 25 years and helped carry out Jazz’s clinical trial. (She has not taken any payments from the company, she said.)Although many of the volunteers reported side effects like nausea, anxiety and dizziness, the change in sleepiness scores was “extremely high,” Dr. Arnulf said. “That’s why we are so enthusiastic with this drug.” These results align, she said, with a 2015 study of a few dozen hypersomnia patients from her clinic who were helped by Xyrem.Other scientists were skeptical of the new trial’s results, which were presented at a scientific conference but not yet published in a journal. Some pointed out that the placebo group’s worsening scores might be at least partly explained by the negative effects of chemical withdrawal from the drug.“Some, or possibly most, of the treatment difference could be contaminated by withdrawal effects,” Mr. Moore of Johns Hopkins said after reviewing a poster presentation of the data the company provided to The New York Times.A senior scientist at Jazz, Dr. Jed Black, said that the volunteers who were switched to placebo did get sleepier, but that their scores were still better than they were before starting the trial, which you wouldn’t expect if they were in the throes of withdrawal. “There’s absolutely no evidence of withdrawal, or any evidence of physical or psychological dependence,” he said.Other experts said it was also hard to tease apart the possible effects of other drugs. More than half of the volunteers had been taking stimulant medications and were allowed to continue those drugs during the study.“Based on what they presented, you cannot say it’s a study that supports approval,” said ​Stanley Edlavitch, an epidemiologist at the University of Missouri Kansas City School of Medicine and former F.D.A. official.But with few other options, many hypersomnia patients are willing to take their chances on the drug. Rebecca King, a board member of the Hypersomnia Foundation, said she long struggled with daytime sleepiness, taking hourslong naps in the morning and afternoon but never feeling like she had slept — until Xyrem, which her doctor legally prescribed “off label” four years ago, before it was approved by the F.D.A.“The doctor actually said to me, ‘Rebecca, are you sure you want to try this? You are messing with your brain,’” she recalled. But the drug, she said, “was a huge, dramatic improvement for me.”Still, it isn’t for everyone. Ms. Ashcraft’s son, for example, saw no benefit when he tried Xyrem.“If you gave me a list of medicines and said, ‘Which one do you want approved for idiopathic hypersomnia?’ I don’t know that I would have picked Xywav,” said Dr. Lynn Marie Trotti, a sleep neurologist at Emory University School of Medicine who has studied the condition.Still, Dr. Trotti is pleased that there is now an approved choice for people with such a debilitating illness.“For some patients, it is going to be the right medication,” she said, “and they should be able to access it.”

The autoimmune disease lupus may be triggered by a defective process in the development of red blood cells (RBCs), according to a study led by researchers at Weill Cornell Medicine. The discovery could lead to new methods for classifying and treating patients with this disease.
The researchers, who published their findings August 11 in Cell, found that in a number of lupus patients, maturing red blood cells fail to get rid of their mitochondria — tiny molecular reactors that help convert oxygen into chemical energy in most cell types, but are normally excluded from red blood cells. This abnormal retention of mitochondria can trigger the cascade of inappropriate and harmful immune activity that is characteristic of the disease.
“Our findings support that red blood cells can play a really important role in driving inflammation in a subgroup of lupus patients,” said senior author Dr. Virginia Pascual, the Drukier Director of the Gale and Ira Drukier Institute for Children’s Health and the Ronay Menschel Professor of Pediatrics at Weill Cornell Medicine. “So this adds a new piece to the lupus puzzle, and could now open the door to new possibilities for therapeutic interventions.”
The lead author of the study was Dr. Simone Caielli, assistant professor of immunology research at the Drukier Institute and the Department of Pediatrics at Weill Cornell Medicine.
Lupus, also known as systemic lupus erythematosus, is a chronic disorder that features intermittent and sometimes debilitating attacks by the immune system on the body’s own healthy tissues, including skin, joints, hair follicles, heart and kidneys. A common underlying factor is the abnormally elevated production of immune-activating proteins called type I interferons. Treatments, which often are taken long-term and have side effects, aim to suppress immune activity, including interferon-driven inflammation. There is no cure for lupus, and how it arises is still largely mysterious. It is estimated to affect roughly 200,000 people in the United States, the vast majority of whom are female.
Previous studies have shown defective mitochondria within immune cells of lupus patients. In the new study, the researchers examined red blood cells, which are supposed to have no mitochondria at all. They found that a large number of lupus patients had red blood cells with detectable levels of mitochondria — and these cells were especially frequent in patients with the most severe lupus symptoms. By contrast, healthy controls had no mitochondria-containing red blood cells.
Dr. Caielli then studied how human red blood cells normally rid themselves of mitochondria as they mature, as prior studies had mainly examined this in mice, and why this process could be defective in lupus patients.
Further experiments revealed how these abnormal red blood cells cause inflammation. In general, as red blood cells age or display signs of damage they are removed by scavenger immune cells called macrophages. Antibodies that bind red blood cells also facilitate their removal. Once ingested by macrophages, the red blood cells’ mitochondrial DNA stimulates a powerful inflammatory pathway called the cGAS/STING pathway, which in turn drives type I interferon production. Underlining the relevance of these findings, “those lupus patients with mitochondria-containing red blood cells and evidence of circulating anti-RBC antibodies had higher interferon signatures compared to those who didn’t,” Dr. Caielli said.
The researchers are now continuing to study the complex process by which mitochondria are retained in red blood cells and end up driving abnormal immune activation. Identifying patients whose lupus symptoms are driven this way might permit to detect when they are likely to undergo lupus flares and to identify specific therapies for them.
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With recent trips to space travel by business moguls like Jeff Bezos and Richard Branson, visiting the edge of space has never been more within the grasp of commercial travel. However, at these altitudes, passengers experience weightlessness, or more generally, altered gravity, that can affect the body’s normal physiology.
In a study, Texas A&M University researchers have used a simulation-based approach to accurately predict the effects of altered gravity on an individual-by-individual basis. Their approach precludes the need for simultaneously testing hundreds of parameters for estimating the cardiovascular state of an individual; rather, it focuses on a handful of significant factors, increasing accuracy and saving time.
“Understanding human physiological responses in altered gravity environments becomes absolutely necessary if we want to push toward new frontiers in space travel,” said Dr. Ana Diaz-Artiles, assistant professor in the Department of Aerospace Engineering. “But no two people are alike, and we need to develop tools to individualize physiological predictions quickly and precisely. Our study addresses that gap.”
The researchers have reported the results of their study in The Journal of Applied Physiology, which was originally published online in April 2021 ahead of final publication in print in June 2021.
Over the millions of years of life on our planet, gravity has been a silent but key influencer on the physiological processes of all living things. Thus, in altered gravity, there is a consequent toll on their physiology. For example, studies have shown that weightlessness makes watering plants difficult, causing waterlogging and preventing growth. In humans, microgravity can also have adverse effects. For example, altered gravity causes bodily fluids to shift toward the head, decreasing circulating blood volume and cardiac atrophy, among other complications.
Detailed investigations of cardiovascular behavior in microgravity have relied on ground-based experiments with human subjects by fastening them onto contraptions that mimic the experience of altered gravity. However, this approach is time-consuming and typically requires an incredibly large pool of subjects. The researchers said an alternate approach is using computer simulations of the cardiovascular system to predict the physiological effects of altered-gravity environments.