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A regimen of pre-surgical immunotherapy and chemotherapy followed by post-surgical immunotherapy significantly improved event-free survival (EFS) and pathologic complete response (pCR) rates compared to chemotherapy alone for patients with operable non-small cell lung cancer (NSCLC), according to results of a Phase III trial reported by researchers at The University of Texas MD Anderson Cancer Center.
The findings, published today in the New England Journal of Medicine, were first presented at the American Association for Cancer Research (AACR) Annual Meeting 2023.
The AEGEAN trial evaluated durvalumab given perioperatively, meaning therapy is given both before and after surgery. Participants on the trial received either pre-surgical (neoadjuvant) durvalumab and platinum-based chemotherapy followed by post-surgical (adjuvant) durvalumab or neoadjuvant placebo and chemotherapy followed by adjuvant placebo.
AEGEAN was the first Phase III trial investigating perioperative immunotherapy in patients with resectable NSCLC to report positive outcomes, and these data add to the growing evidence supporting the benefits of both neoadjuvant and adjuvant immunotherapy for these patients
“Our goal is to increase cures for lung cancer. Throughout decades of research with adjuvant and neoadjuvant chemotherapy, we only succeeded in increasing cures by around 5%,”
said principal investigator John Heymach, M.D., Ph.D., chair of Thoracic/Head & Neck Medical Oncology at MD Anderson. “This one study alone has the potential to increase that percentage significantly, and we look forward to many more improvements going forward.”
Of the patients receiving perioperative durvalumab, 17.2% had a pCR compared to just 4.3% of those receiving chemotherapy alone. At the first interim analysis of EFS, with a median follow-up of 11.7 months, the median EFS was 25.9 months in the placebo arm, but it had not yet been reached in the durvalumab arm.

A team of researchers has developed a software tool called DANGER (Deleterious and ANticipatable Guides Evaluated by RNA-sequencing) analysis that provides a way for the safer design of genome editing in all organisms with a transcriptome. For about a decade, researchers have used the CRISPR technology for genome editing. However, there are some challenges in the use of CRISPR. The DANGER analysis overcomes these challenges and allows researchers to perform safer on- and off-target assessments without a reference genome. It holds the potential for applications in medicine, agriculture, and biological research.
Their work is published in the journal Bioinformatics Advances on August 23, 2023.
Genome editing, or gene editing, refers to technologies that allow researchers to change the genomic DNA of an organism. With these technologies, researchers can add, remove or alter genetic material in the genome.
CRISPR-Cas9 is a well-known gene editing technology. It has a reputation for being more accurate, faster, and less expensive than other similar technologies. However, gene editing using CRISPR technology presents some challenges. The first challenge is that the phenotypic, or observable, effects caused by unexpected CRISPR dynamics are not quantitatively monitored.
A second challenge is that the CRISPR technology generally depends on basic genomic data, including the reference genome. The reference genome is like a template that provides researchers with general information on the genome. Unexpected sequence editing with mismatches can occur. These off-target sites are always unexpected. So researchers need a way to observe factual genomic sequences and limit potential off-target effects. “The design of genome editing requires a well-characterized genomic sequence. However, the genomic information of patients, cancers, and uncharacterized organisms is often incomplete,” said Kazuki Nakamae, an assistant professor of the PtBio Collaborative Research Laboratory at the Genome Editing Innovation Center, Hiroshima University.
The research team set out to devise a method to deal with the issues of the phenotypic effects and the dependence on a reference genome. The team’s DANGER analysis software overcomes these challenges. The team used gene-edited samples of human cells and zebrafish brains to conduct their risk-averse on- and off-target assessment in RNA-sequencing data.
The team demonstrated that the DANGER analysis pipeline achieves several goals. It detected potential DNA on- and off-target sites in the mRNA-transcribed region on the genome using RNA-sequencing data. It evaluated phenotypic effects by deleterious off-target sites based on the evidence provided by gene expression changes. It quantified the phenotypic risk at the gene ontology term level, without a reference genome. This success showed that DANGER analysis can be performed on various organisms, personal human genomes, and atypical genomes created by diseases and viruses.
The DANGER analysis pipeline identifies the genomic on- and off-target sites based on de novo transcriptome assembly using RNA-sequencing data. A transcriptome includes a collection of all the active gene readouts in a cell. With de novo transcriptome assembly, the transcriptome is assembled without the help of a reference genome. Next, the DANGER analysis identifies the deleterious off-targets. These are off-targets on the mRNA-transcribed regions that represent the downregulation of expression in edited samples compared to wild-type ones. Finally, the software quantifies the phenotypic risk using the gene ontology of the deleterious off-targets. “Our DANGER analysis is a novel software that enables quantifying phenotypic effects caused by estimated off-target. Furthermore, our tool uses de novo transcriptome assembly whose sequences can be built from RNA-sequencing data of treated samples without a reference genome,” said Hidemasa Bono, a professor at the Genome Editing Innovation Center, Hiroshima University.
Looking ahead, the team hopes to expand their research using the DANGER analysis. “We will apply the software to various genome editing samples from patients and crops to clarify the phenotypic effect and establish safer strategies for genome editing,” said Nakamae.
DANGER analysis is open-source and freely adjustable. So the algorithm of this pipeline could be repurposed for the analysis of various genome editing systems beyond the CRISPR-Cas9 system. It is also possible to enhance the specificity of DANGER analysis for CRISPR-Cas9 by incorporating CRISPR-Cas9-specific off-target scoring algorithms. The team believes that the DANGER analysis pipeline will expand the scope of genomic studies and industrial applications using genome editing.

In a carpeted office suite, Alex Beck settled onto a mattress and, under the watch of a trained guide, began chomping through a handful of “Pumpkin Hillbilly” mushrooms.A Marine Corps veteran who was sexually assaulted during his time in the armed forces, Mr. Beck had long been searching unsuccessfully for a way to put those nightmarish years behind him. Now he was ready for a different kind of journey, a psychedelic trip through the nether regions of his own mind.As he felt his thoughts starting to spin, his “facilitator,” Josh Goldstein, urged him to surrender and let the mushrooms guide him.“It’s like the idea of planting a seed and then letting it go,” he said. Stigmatized in law and medicine for the past half-century, psychedelics are in the midst of a sudden revival, with a growing body of research suggesting that the mind-altering compounds could upend psychiatric care. Governments in several places have cautiously started to open access, and as Oregon voters approved a broad drug decriminalization plan in 2020, they also backed an initiative to allow the use of mushrooms as therapy. This summer, the state debuted a first-of-its-kind legal market for psilocybin mushrooms, more widely known as magic mushrooms. Far from the days of illicit consumption in basements and vans, the program allows people to embark on a therapeutic trip, purchasing mushrooms produced by a state-approved grower and consuming them in a licensed facility under the guidance of a certified facilitator.Mr. Beck, 30, was one of the first clients at a facility in the central Oregon city of Bend that began conducting sessions this summer in a building that on other days of the week offers chiropractic services. In his youth, Mr. Beck had experimented with psychedelics for recreation. But as he struggled with his lingering post-traumatic stress in adulthood, he learned about what seemed to be promising new research into plant-based psychedelics for mental health issues that did not respond to other treatments. He wondered if they could help him clear his head from the horrors of the past.Ryan Reid, the operations director at Bendable Therapy in Bend, Ore., prepared to deliver psilocybin mushrooms for a guided psychedelic treatment.Amanda Lucier for The New York Times Alex Beck, right, a Marine Corps veteran suffering from post-traumatic stress, and Josh Goldstein, a psilocybin facilitator, before Mr. Beck’s psychedelic treatment.Amanda Lucier for The New York Times“I’m trying to reset my brain to where I can look at life in a new way,” he said.Plants and fungi with psychoactive properties have been used for thousands of years. More modern uses in the United States grew in the 1950s with promising research on LSD and psilocybin, and the substances soon became a signature of the counterculture movement, so much so that political leaders moved to criminalize their use and halt research into their effects.In altering the normal activity of the brain, psilocybin has the power to distort perceptions, transform senses and bend emotions. Researchers see the possibility of bestowing the brain with new elasticity, allowing people a chance to escape mental ruts. Studies have suggested that breakthroughs may be possible for people with challenging mental health conditions, including PTSD, substance addiction and treatment-resistant depression, without the habit-forming properties of some other drugs. For those who have long worked on psychedelics research, the sudden expansion in access in Oregon and Colorado, along with cities like Denver, Detroit, Minneapolis and Washington, D.C., have prompted a mix of elation and trepidation. Oregon has settled on a middle-of-the-road approach, requiring neither a doctor’s supervision nor a specific medical diagnosis, but providing for strict oversight of supply and use.Dr. Janis Phelps, director of the Center for Psychedelic Therapies and Research at the California Institute of Integral Studies, said she and other researchers had been wary of the decriminalization movement. Many in the field had worked for years to remain strictly scientific, hoping to avoid government crackdowns, and to give the U.S. Food and Drug Administration time to fully review the effects of psilocybin before pressing ahead with efforts to make it legal.“I have changed my mind,” she said. While she remains concerned that bad actors could try to enter the industry strictly for profit, or try to take advantage of vulnerable people, she has come to believe that the open door in Oregon could advance the use of psychedelics in ways that methodical approaches cannot.Dr. Charles Nemeroff, the chair of the department of psychiatry and behavioral sciences at the University of Texas at Austin, said he continues to be wary. Psilocybin is powerful, with immediate effects lasting for hours, and uncertain outcomes for patients, he said, recalling one patient of his who has experienced protracted psychosis, losing partial connection to reality, after taking doses of mushrooms. The treatments ruined her life, said Dr. Nemeroff, who said he worried about the lack of required medical oversight in Oregon’s program.Researchers believe psilocybin can be used to treat mental health conditions, including PTSD, substance addiction and treatment-resistant depression.Mason Trinca for The New York TimesGared Hansen grows psilocybin at Uptown Fungus, one of five psilocybin manufacturers in the state, outside of Springfield, Ore.Mason Trinca for The New York Times“I’m really uncomfortable with this,” he said, adding that it could erase progress the field has made. “We’ll end up back in the Nixonian era in which psychedelics could not even be studied.”While some form of legalized marijuana is authorized in all but 12 states, creating a huge, multi-billion-dollar industry, the psilocybin market remains small, with an uncertain financial outlook for those entering it. Only five businesses are approved to manufacture the therapeutic-use fungi in Oregon, with 13 sites approved to host dosing sessions.Bend is home to two of them. One offers a treatment experience that costs as much as $15,000, including several days spent getting to know the facilitator and the townhome-like space where the treatment takes place. Mr. Beck, who lives in Bend, connected with another organization known as Bendable, a nonprofit that helps coordinate treatment and asks clients to pay what they can afford.A single session costs about $3,000, which includes a preparatory meeting, a guided session with the mushrooms that lasts several hours, and a follow-up appointment a few days later in which the client discusses lessons from the session and how to integrate them into their other therapy.Amanda Gow, the executive director of Bendable, said she opens her email each day to messages from all over the country: a woman in Kentucky desperate for help with her husband’s PTSD, a father in western Oregon willing to try anything to help his adult son’s depression, a single mother in Bend struggling with childhood trauma.Many described years of therapy, medical visits and antidepressants but little progress. The wait list includes hundreds of people.Officials in other states are watching what happens in Oregon. Voters in Colorado approved a measure last year to decriminalize psilocybin and to set the state on the path to a legal therapeutic market. In other states, including Texas, lawmakers have authorized studies of psilocybin for treating ailments such as PTSD. The F.D.A. has granted the drug “breakthrough therapy” status, which allows for expedited review of substances that have demonstrated substantial promise.Bjorn Fritzsche, center, a senior chemist and research engineer, preparing to test a batch of psilocybin at Rose City Laboratories in Portland, Ore.Mason Trinca for The New York TimesPsilocybin is tested for potency and purity.Mason Trinca for The New York TimesBut there is uncertainty about the best path forward. California lawmakers approved a bill this year to decriminalize several hallucinogens, but Gov. Gavin Newsom vetoed the measure, saying the state needs to first set up regulated treatment guidelines. The American Psychiatric Association has urged caution, saying treatments should be limited to research studies for now. Mr. Goldstein, who works with Bendable and guides sessions for clients, had his first psychedelic experience more than three decades ago and spent recent years facilitating underground mushroom sessions. He does not have a medical degree but previously worked as an academic director at a therapeutic boarding school.Not all of the sessions he has supervised have been pleasant. One client, Mr. Goldstein said, recently had her first psychedelic session and hated it, asking for it to end soon after it began. It lasted six hours. He said such experiences highlight the importance of guided sessions, with someone able to help people navigate the experience. Even a difficult session, he said, can help clients gain insight into why they were struggling so much with what was on their mind.“Those can be better than the people who just see rainbows and unicorns,” he said.For his treatment session, Mr. Beck arrived in the morning to the office suite. Mr. Beck lit a candle and Mr. Goldstein put on a playlist of music that traces an arc of a psilocybin experience, beginning with calming tracks with titles such as “Flute Traveller” and “Unlocking the Doors of Eternity.”Once the mushrooms took hold, as Mr. Beck described it later, he felt himself beginning to thrash, but Mr. Goldstein said he had remained largely calm. Mr. Beck recalled visions of colorful strands of ribbon floating through his mind, wrapping themselves around different issues that he had prepared himself to tackle — the sexual assault, the PTSD, various difficult relationships.Alex Beck, right, met with his psilocybin facilitator, Josh Goldstein, for a post-treatment counseling session.Amanda Lucier for The New York TimesMr. Beck at his home in Bend after the treatment. “I had been holding on to so many traumas and issues,” he said. “It was like a massive weight had been released.”Amanda Lucier for The New York TimesAs the mushrooms began to wear off after several hours, he was tearful. He told Mr. Goldstein about realizing how important family was to him. For the first time, he said, he decided he wanted to have children of his own some day.The following day, Mr. Beck and Mr. Goldstein met at a park to discuss the experience and how to integrate it into Mr. Beck’s more traditional therapy. “I had been holding on to so many traumas and issues,” Mr. Beck said. “It was like a massive weight had been released.”Still, there is more to do. Mr. Beck continues in his traditional therapy and plans to increase the frequency of those sessions, which he has found productive with more clarity about what needs to be discussed. The treatments have complemented each other, he said. “I wouldn’t say it’s a ‘one and done, I’m completely cured,’” he said. “It takes work.”

A decade ago, Hadley Vlahos was lost. She was a young single mother, searching for meaning and struggling to make […]

Drug companies are making billions from a new class of in-demand weight-loss treatments. But the prices are not what they seem.The problem is daunting: Powerful but expensive new drugs could help many of the 100 million American adults who have obesity and alleviate a grave public health concern.But how can the nation afford lifelong treatments for so many people, with sticker prices for each patient ranging from about $900 to $1,300 every four weeks?Some researchers, like Dr. Walter C. Willett, professor of epidemiology and nutrition at the Harvard T.H. Chan School of Public Health, have warned that the drugs could add 50 percent to the country’s health care spending.“You can see this ballooning completely out of control,” he said.But there is one factor often left out of these discussions: The drugs’ list prices are generally very different from the net prices, which companies receive after making secret deals with health insurers or the intermediaries known as pharmacy benefit managers. Companies generally do not reveal net prices, but there are data sources that can be used to estimate them.A recent paper published by the American Enterprise Institute revealed that the net prices for the new obesity drugs are just a fraction of the published annual list prices.And while the drugs’ prices remain out of reach for many, economists anticipate they will soon be driven down. More than a dozen companies are developing obesity drugs. As they enter the market, greater choice is expected to make prices plummet, as has happened with other expensive drugs.“My prediction is that as competition increases, prices will decrease accordingly,” said Jalpa Doshi, professor of medicine and director of the economics evaluation unit at the University of Pennsylvania.Strong Demand, Falling Prices?For now, manufacturers are reaping the rewards of soaring demand.Investors expect Novo Nordisk, the manufacturer of Wegovy, to earn $4 billion in revenue this year. The company’s other drug, Ozempic, is expected to bring in $11 billion. The drugs are driving such a bonanza that they account for almost all of the latest economic growth in Denmark, the home of Novo Nordisk.Those revenues are based on the net prices.For their analysis, Benedic N. Ippolito, an economist at the American Enterprise Institute, and Joseph F. Levy, a health economist at Johns Hopkins Bloomberg School of Public Health, relied on data from SSR Health, which uses company financial filings and estimates of the number of prescriptions filled.The economists derived net prices by using data from SSR Health for the second quarter of 2022 through the first quarter of 2023. The exception is Mounjaro, made by Eli Lilly, for which only data from the first quarter of 2023 was available.Net prices, the revenue divided by the number of prescriptions in their analysis, appear to be around $700 every four weeks for Wegovy, or about $650 less than the list price; about $300 for Ozempic, or nearly $650 less than the list price; and approximately $215 for Mounjaro, or about $800 less than its list price.That means Wegovy’s net price is about half of its list price, Ozempic’s is nearly two-thirds lower and Mounjaro’s net price is nearly 80 percent lower than its list price.Dr. Ippolito cautioned that because prices and prescriptions are in flux, these figures might change over time, but added that “these estimates give a good sense for the likely amount paid by many insurers and give a good sense for the amount of discounting going on.”Pragya Kakani, an economist at Weill Cornell Medical College, analyzed similar data with similar results but was not involved in Dr. Ippolito and Dr. Levy’s research.Novo Nordisk’s other drug, Ozempic, is expected to bring the company $11 billion.Tom Little/ReutersCraig Garthwaite, a health care economist at Northwestern University, is especially intrigued by the net prices of Ozempic and Mounjaro. Both are approved for people with diabetes but also cause weight loss. Wegovy, the same drug as Ozempic, is approved for weight loss. But the price of Ozempic is substantially lower than Wegovy’s price.The reason may be that Ozempic has a direct competitor in Mounjaro.But even Wegovy, which so far has the market for the new obesity drugs to itself, has an unexpectedly low net price, Amitabh Chandra, a health care economist at Harvard, said.“One might have naïvely thought that these are new medicines that are in great demand, so rebates would be small to nil,” Dr. Chandra said.“I was shocked,” he said, “by the extent of the rebates.”A Price We Already PayOne question looms, experts say: What is weight loss worth to patients and society?Obesity itself is expensive because it increases the risk for expensive diseases like diabetes and heart disease. One study found that obesity was associated with $1,861 excess yearly health costs per person, accounting for $172.74 billion in annual extra costs.The Institute for Clinical and Economic Review, an influential nonprofit group, asked about a year ago if the new weight-loss drugs are cost-effective, meaning that their value in terms of a better quality of life, a longer life and benefit to society exceeds their cost.Wegovy, the group reported, was not cost-effective. But the institute relied on an early and less precise estimate of the drug’s net price.When shown Wegovy’s estimated net price in the A.E.I. research, the group’s chief medical officer, Dr. David M. Rind, said that if the calculations were correct, Wegovy was cost-effective but “still poses major budget challenges.”Ozempic’s price is substantially lower than Wegovy’s price, which may be because Ozempic has a direct competitor in Mounjaro. George Frey/ReutersDr. Willett, of Harvard, added in an interview: “I don’t think anyone can predict exactly where this will go because competition may reduce prices, and the uptake is still not clear, but the potential cost could go way beyond anything we have seen.”Still, the expectation is that with less obesity, there will be fewer expensive obesity-related health problems, including type 2 diabetes.Not only can diabetes lead to kidney failure, blindness and amputations, it also doubles the risk for heart attacks and strokes.Patients may also get relief from the extreme social stigma and, often, self-loathing that accompanies obesity.Until recently, the idea that treating obesity would reduce obesity-related health risks was based on anecdotes and correlations, not cause and effect.Then in August Novo Nordisk announced the results of a large study, showing that Wegovy can reduce the risk of heart attacks, strokes, hospitalizations for heart failure and heart disease deaths by 20 percent.That outcome alters the picture, Dr. Garthwaite said.Some insurers do not cover drugs like Wegovy and may view obesity medications as vanity drugs. In response, some patients are suing their insurers.With a cardiovascular benefit, he said, that rationale for not covering the drugs is “out the window.”Costs We Can’t All AffordWhile the net prices of the drugs may be lower than expected, they remain too expensive for many potential patients.Those on Medicare, for instance, have no insurance coverage for Wegovy because Medicare is prevented by law from covering weight-loss drugs. Few state Medicaid programs cover the drug.And while Novo Nordisk says that 80 percent of private insurers cover Wegovy, the drug is not affordable for all insured patients.Katherine Baicker, a health economist, provost at the University of Chicago and an Eli Lilly board member, said that cheaper health insurance includes co-pays and deductibles that often render Wegovy out of reach. Patients with low-premium plans offered through the Affordable Care Act would similarly be priced out.A large study by Novo Nordisk showed that Wegovy can reduce the risk of heart attacks, strokes, hospitalizations for heart failure and heart disease deaths by 20 percent.Tom Little/ReutersDr. Scott Ramsey, a health economist at Fred Hutchinson Cancer Center, worries that poorer patients, who are uninsured or whose insurance requires high co-pays, will be looking on longingly as wealthier patients get the drugs.“We spent 15 years talking about the soaring cost of obesity to the health care system,” Dr. Garthwaite, the Northwestern economist, added. But with a way to cut that cost in reach, he said the attitude of some insurers seems to be, “we don’t want you to come up with a fix that costs money.”Waves and PeaksRelief should be coming soon, health economists predict, with companies rushing to develop their own drugs. Competition may lead to lower prices.That happened, for example, with drugs for hepatitis C. An effective cure for the liver disease initially cost as much as $84,000, leading to dire warnings that the cost would be comparable to “total spending in the United States on all drugs.”The list price of the hepatitis C treatment plunged, as competitors entered the market. Pharmacy benefit managers, which negotiate with drug makers, had more leverage as companies competed. Net prices fell accordingly.A similar scenario may play out with Wegovy, which “is riding the wave of not having any direct competition,” Dr. Doshi said. But that status will end soon.A version of Mounjaro by Eli Lilly is expected to be approved this year for obesity — a potential opening for insurers to agree to cover Wegovy but not Mounjaro, for example, if Wegovy’s price were to be sufficiently reduced.Dr. Ippolito added that with more than 70 obesity drugs in development, he expected that competition would only increase.For now, although the price of the drugs is likely at its peak, Dr. Chandra, the Harvard health care economist, argued that it is imperative for access to the drugs to be increased, even if that imposes a cost to society.The purpose of health insurance is not to save money, he said, but “to improve the quality of life, happiness and self-esteem.”

Over the last two decades, medical facilities and staff have become casualties of war more frequently, in violation of international law.The explosion at the Ahli Arab Hospital in Gaza City on Tuesday was the latest in a growing series of violent incidents involving medical facilities in conflict zones, which together have taken an enormous toll on vital health care infrastructure and staff in violation of what was once a bedrock aspect of international law.Over last two decades, as the principle of sparing health care workers and facilities has continually eroded, the most dangerous incidents have been carried out by state actors, said Michiel Hofman, who is an operational coordinator for Doctors Without Borders in Sudan and a veteran of medical aid delivery in Afghanistan, Yemen and Syria.Yet Article 18 of the First Geneva Convention, ratified by United Nations member states after World War II, says that civilian hospitals “may in no circumstances be the object of attack, but shall at all times be respected and protected by the parties to the conflict.”Article 20 of the convention says that health care workers similarly must be protected by all sides.“The willingness of states to push the boundaries of international humanitarian law seems to have accelerated,” Mr. Hofman said. “It’s the states that have explicitly signed the Geneva Conventions, and states usually have far greater military power and especially air power.”The two sides traded blame for the explosion at the hospital in Gaza City.Mohammed Saber/EPA, via ShutterstockIn Ukraine, Russia has carried out more than 1,100 attacks on health care facilities and personnel since it began its invasion 21 months ago, a staggering number for so short a period, said Leonard Rubenstein, an expert in health and human rights at Johns Hopkins University.Mr. Rubenstein chairs the Safeguarding Health in Conflict Coalition, which is made up of more than three dozen human rights and humanitarian organizations working in conflict zones, tracking attacks on health care around the world.Mr. Rubenstein said the pattern of Russian attacks showed that Moscow has in some cases intentionally targeted hospitals and in others indiscriminately attacked areas where hospitals were located; both are war crimes. “They’re unaccountable, with complete impunity,” he said. “And they don’t care.”Neither Russian soldiers or commanders nor any other state or paramilitary actor that has attacked medical sites, with one exception, has ever faced prosecution by international bodies, he added: “There is wide agreement in the international community that attacks on health care are unacceptable — protection of health care is like motherhood and apple pie. But there’s no real commitment by governments to do what you need to do to stop it.”He added: “There has been no accountability, instead complete impunity — no prosecution and political interference with U.N. entities that seek even mild condemnation of states responsible for attacks.”The only time a deliberate attack on a hospital was ever referred for prosecution in an international court involved the war in Bosnia. The charge was one of seven against a Serbian military commander considered by the tribunal investigating war crimes in the former Yugoslavia.The International Criminal Court, a tribunal set up by the United Nations 21 years ago to prosecute crimes against humanity, has never issued an indictment for an attack on medical personnel or infrastructure.A strike in March 2022 hit a maternity hospital in Ukraine.Evgeniy Maloletka/Associated PressAttacks on medical facilities jeopardize health care not only for those injured by fighting, but also for all those with routine medical needs. On Thursday, Doctors Without Borders (also known as M.S.F., an abbreviation for its French name, Médecins Sans Frontières) withdrew a surgical team from a hospital in Sudan after military authorities blocked all delivery of supplies to the facility. The team had been providing lifesaving trauma surgeries and cesarean sections from one of the last functioning hospitals in the capital, Khartoum.“It’s so painful, because of the moral distress of the medics,” Mr. Hofman said. They were unable to function without basic supplies, but also profoundly disturbed to cut off one of the last sources of care in a city where fighting has not let up since rival factions of the military government went to war in April.In Ukraine, Russian attacks have destroyed 10 to 15 percent of medical facilities. The damage is even more far-reaching than it might seem, said Pavlo Kovtoniuk, a former deputy minister of health in Ukraine who now works with a think tank called the Ukrainian Health Center.“Hospitals symbolize respect for civilian life, and when people see that disregarded they say, ‘We have to get out,’” he said. “We have a huge loss of human capital, with more than six million people now living outside the borders.”Among those who remain, there is a growing population in need of rehabilitation and psychosocial support, from a steadily shrinking health system.“This is not a situation of waging war according to the laws of war and the Geneva Convention — this is a completely different philosophy of war where civilian lives are disregarded entirely,” Mr. Kovtoniuk said.He added: “We are revisiting the rules we thought were a given on regard for civilian life, and Russia has contributed to this feeling, ‘OK, we can do this. We can attack civilian infrastructure as a weapon of war.’”Ukrainian officials are working with the International Criminal Court to compile evidence from the attacks, Mr. Kovtoniuk said. At least some top Russian officials must be indicted in order to re-establish the principle of protecting health care workers and facilities, he said. Russia has often either said that the facilities it hit were harboring Ukrainian fighters or dismissed the accusations as fake.In Sudan, M.S.F. says that fatalities caused by neglected medical needs are as great as those caused by violent injuries. According to the World Health Organization, 70 percent of Sudan’s medical facilities are no longer functioning. More than seven million people are now internally displaced and face a cascade of disease outbreaks.The World Health Organization says vaccine delivery is impossible in much of Sudan.Agence France-Presse, via Getty ImagesThere are epidemics of cholera, malaria, dengue fever and measles in Sudan. The W.H.O. says measles and malnutrition have killed 1,200 children since the war began in April, and vaccine delivery is impossible in many parts of the country.“Health care was terrible to begin with, and any specialized care we had was overwhelmingly centered in Khartoum and it’s no longer functioning,” said Dr. Yasir Yousif Elamin, president of the Sudanese American Physicians Association. “The places able to do cardiac surgery, neurosurgery, cancer care, dialysis — all of these are out of service now.”People who need these services are scattering to areas far from the capital; patients who need dialysis three times a week are receiving it once in a 10-day stretch, while cancer patients might manage to find chemotherapy treatment every few months, he said.The physicians’ association is tracking attacks on health care facilities in hopes of supporting eventual prosecution.Last month, in the city of Wad Madani, Dr. Elamin met a 5-year-old child who had been shot in the abdomen in Khartoum. His mother had taken him hundreds of miles in search of help.“Imagine you don’t have something as basic as this, for a boy hit accidentally,” Dr. Elamin said.Researchers began tracking attacks on health care facilities in conflict zones in an organized fashion only in the early 2000s, so it is difficult to speak with much certainty about the trend, Mr. Rubenstein said.But in an analysis of the figures for 2022, Safeguarding Health in Conflict said that the 1,989 incidents that were tabulated represented “by far the highest number” documented since the coalition began reporting a decade ago.After Ukraine, which accounted for nearly half the incidents, the most-affected country was Myanmar. More than 800 health care workers have been arrested there since a military coup in 2021.Between 2014 and 2016, there was a series of horrific bombings of medical facilities in Afghanistan, Syria and Yemen — including a U.S. airstrike on an M.S.F.-run trauma center in Kunduz, Afghanistan, in 2015 that killed 42 people. (The Pentagon called it “unintentional.”)The aftermath of a United States airstrike on the Doctors Without Borders hospital in Kunduz, Afghanistan, which killed 42 people.Victor J. Blue for The New York TimesThe violence prompted the U.N. Security Council to unanimously adopt a resolution calling for greater protection of health care workers and facilities in armed conflict, which brought “a bit of a breather,” Mr. Hofman said. Those kinds of airstrikes continued in Syria, however.“But now with four major wars erupting in the last few years — Ethiopia, then Ukraine, Sudan, and now Gaza — we are at a peak again,” he said.There have been more than 115 attacks on health care facilities and personnel in the West Bank and Gaza Strip since the Oct. 7 Hamas attacks. Israel has warned 20 hospitals in the north of Gaza to evacuate their patients in anticipation of a ground invasion but Palestinian doctors say it is impossible to move them.In 2009, a suicide bomber infiltrated a graduation ceremony for medical students in Mogadishu, the Somali capital, and killed three cabinet ministers who were in attendance, plus the dean of the medical school, a dozen students and two journalists.In addition to the terrible loss of life, the International Committee of the Red Cross calculated that an indirect effect of those deaths was as many as 150,000 missed physician consultations per year, in a country where the medical system was already in tatters because of a decades-long civil war.

Published2 days agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Smitha MundasadHealth reporter More support is needed to prevent babies and young children developing mental health problems in later life, leading doctors say.Their report shows there is growing evidence that intervening very early on – from conception to the age of five – may help stop conditions arising or worsening. The Royal College of Psychiatrists is calling for more specialist services. The government says the mental health of children and parents is paramount.Officials say they are investing more in expanding NHS services, alongside funding programmes designed to support children and caregivers.NHS data shows about 5% of two to four-year-olds struggle with anxiety, behavioural disorders and neurodevelopmental conditions including ADHD. The Royal College of Psychiatrists’ report suggests half of mental health conditions arise by the age of 14, and many start to develop in the first years of life, making early action “vital”.Dr Trudi Seneviratne, from the Royal College of Psychiatrists (RCPsych), said the majority of under-fives with mental health conditions were not receiving the level of support needed “to help them become productive, functioning adults and reach their full potential”.She added: “The period from conception to five is essential in securing the healthy development of children into adulthood. “Unfortunately, these years are often not given the importance they should be, and many people are unaware of what signs they should be looking out for. “Parents, carers and society as a whole have a critical role to play. This includes securing positive relationships and a nurturing environment that supports the building blocks of a child’s social, emotional and cognitive development.”Dr Seneviratne says anyone concerned about a child’s persistent behavioural issues or eating and sleeping problems should seek health advice. RCPsych experts suggest a number of ways to prevent mental health issues in babies and children, including providing support for the mother in pregnancy, working with parents to promote attachment to their child and recommending parenting programmes in the early stages of a child’s life. They say many factors can increase the risk of problems developing in childhood, such as alcohol or substance misuse during pregnancy and adverse experiences in childhood including domestic violence, physical and emotional neglect and abuse. The report’s recommendations include:New specialist services across the UK for under-fives, their parents and carers, with timely access to a team of people including speech and language therapy, psychologists and social workersMore training for healthcare workers on how to spot and support under-fives with mental health problemsMore research on the best ways to help young childrenBetter data collection on young children experiencing problemsSupport to help the wider population gain a greater understanding about mental health of under-fivesThe wide-ranging report is backed by a number of organisations including Unicef UK, the Royal College of Paediatrics and Child Health, and the Royal College of Obstetricians and Gynaecologists.Joanna Moody, from Unicef UK, said: “Mental health in infancy and early childhood is often overlooked, yet it lays the foundations for a child’s future.”She said the report provided “a strong evidence base for action to prioritise mental health right from the start of children’s lives”.She added many services have a “vital role” in supporting children’s mental health, including early education, social services, maternity, health visiting and primary care.If you have been affected by any of the issues raised in this story you can visit BBC Action Line.More on this storyHuge leap in children in mental health crisisPublished4 February 2022Quarter of 17-19-year-olds may have mental disorderPublished29 November 2022Mental health patients ‘at risk’ in child wardsPublished25 May

Cannabis use, even for medical purposes, could make some people sick due to harmful fungi that contaminate the plants.
That is the finding of a recently published peer-reviewed journal article, whose authors recommend further study and consideration of changes to regulations to protect consumers, especially those who are immunocompromised. They examined data, previous studies, and U.S. and international regulations related to the cannabis and hemp industry.
The article was published in Frontiers in Microbiology. It was researched and written by Kimberly Gwinn, professor of entomology and plant pathology at the University of Tennessee Institute of Agriculture: Maxwell Leung, assistant professor, and Ariell Stephens, graduate student, both from the School of Mathematical and Natural Sciences at Arizona State University; and Zamir Punja, professor of plant pathology/biotechnology at Simon Fraser University, Burnaby, British Columbia, Canada.
“Hemp and cannabis are new crops, and we are in the early stages of understanding relationships with their pathogens. Several pathogens produce mycotoxins, compounds that negatively impact human health and are regulated in other crops. In this review, we summarize the current literature on mycotoxins in hemp and cannabis products, identify research gaps in potential mycotoxin contamination in hemp and cannabis, and identify potential developments based on research in other crop systems,” Gwinn said.
Cannabis research has mostly focused on the substance and medical uses of the plant, but with the increased legalization of cannabis for various uses, this article addresses the need for more study of potential health risks.
“Although fungi and mycotoxins are common and well-studied contaminants in many agricultural crop species, they have been generally under-studied in cannabis and hemp. This is partly because human health risk assessment methodologies used to regulate food and pharmaceuticals have yet to become standard for the emerging cannabis and hemp industries. Additionally, the wide range of consumer uses of cannabis and hemp flowers, including for medical use by patients with susceptible conditions, makes it uniquely challenging to assess and manage human health risk of these contaminants,” according to the article.
The authors discuss Aspergillus, Penicillium, Fusarium, Mucor, and other fungi that can infect the plants and can produce mycotoxins; review the regulations and assessment methods of the contaminants; and offer recommendations to produce safer products for all consumers. Environmental factors such as where the plants are grown, whether indoors or outdoors, and in soil or soilless media, may impact the kinds of contaminants and ensuing health risks.

Millions of couples worldwide experience infertility with half of the cases originating in men. For 10% of infertile males, little or no sperm are produced. Now, new research from the Stowers Institute for Medical Research, in collaboration with the Wellcome Centre for Cell Biology at the University of Edinburgh, is shedding light on what may be going wrong in the process of sperm formation, leading to potential theories on possible treatments.
“A significant cause of infertility in males is that they just cannot make sperm,” said Stowers Investigator Scott Hawley, Ph.D. “If you know exactly what is wrong, there are technologies emerging right now that might give you a way to fix it.”
The study published on October 20, 2023, in Science Advances from the Hawley Lab and Wellcome Centre Investigator Owen Davies, Ph.D., may help explain why some men do not make enough sperm to fertilize an egg. In most sexually reproducing species, including humans, a critical protein structure resembling a lattice-like bridge needs to be built properly to produce sperm and egg cells. The team led by former Postdoctoral Research Associate Katherine Billmyre, Ph.D., discovered that in mice, changing a single and very specific point in this bridge caused it to collapse, leading to infertility and thus providing insight into human infertility in males due to similar problems with meiosis.
Meiosis, the cell division process giving rise to sperm and eggs, involves several steps, one of which is the formation of a large protein structure called the synaptonemal complex. Like a bridge, the complex holds chromosome pairs in place enabling necessary genetic exchanges to occur that are essential for the chromosomes to then correctly separate into sperm and eggs.
“A significant contributor to infertility is defects in meiosis,” said Billmyre. “To understand how chromosomes separate into reproductive cells correctly, we are really interested in what happens right before that when the synaptonemal complex forms between them.”
Previous studies have examined many proteins comprising the synaptonemal complex, how they interact with each other, and have identified various mutations linked to male infertility. The protein the researchers investigated in this study forms the lattices of the proverbial bridge, which has a section found in humans, mice, and most other vertebrates suggesting it is critical for assembly. Modeling different mutations in a potentially crucial region in the human protein enabled the team to predict which of these might disrupt protein function.
The authors used a precise gene editing technique to make mutations in one key synaptonemal complex protein in mice, which allowed the researchers, for the first time, to test the function of key regions of the protein in live animals. Just a single mutation, predicted from the modeling experiments, was verified as the culprit of infertility in mice.

Stimulating muscle fibers with magnets causes them to grow in the same direction, aligning muscle cells within tissue, Massachusetts Institute of Technology (MIT) and Boston University investigators report October 20 in the journal Device. The findings offer a simpler, less time-consuming way for medical researchers to program muscle cell alignment, which is strongly tied to healthy muscle function.
“The ability to make aligned muscle in a lab setting means that we can develop model tissues for understanding muscle in healthy and diseased states and for developing and testing new therapies that combat muscle injury or disease,” says senior author Ritu Raman, an MIT engineer. A better understanding of the rules that govern muscle growth could also have applications in robotics, she adds.
In a previous investigation, Raman and colleagues found that “exercising” muscle fibers by making them contract in response to electrical stimulation for 30 minutes a day over the course of 10 days made the fibers stronger. This time, the researchers wanted to explore whether mechanically stimulating the muscle fibers over the same time frame (rather than letting them respond on their own) would have the same result. To investigate, they developed a method to mechanically stimulate muscle tissue that differs from typical lab techniques.
“Generally, when people want to mechanically stimulate tissues in a lab environment, they grasp the tissue at both ends and move it back and forth, stretching and compressing the whole tissue,” said Raman. “But this doesn’t really mimic how cells talk to each other in our bodies. We wanted to spatially control the forces between cells within a tissue, matching native systems.”
To stimulate the muscle cells in a more true-to-life way, Raman and her team grew cells in a Petri dish on a soft gel that contained magnetic particles. When they would move a magnet back and forth under the gel, the particles moved back and forth, too, which “flexed” the cells. The researchers could precisely control the way the gel moved, and, in turn, the magnitude and direction of the forces the cells within experienced, by changing the strength and orientation of the magnet. To measure the alignment of the muscle fibers within the tissues and whether they contracted in synchrony, the team’s collaborators at Boston University developed a custom software that automatically tracked videos of the muscle and generated graphs of its movement.
“We were very surprised by the findings of our study,” said Raman. While mechanically stimulating the muscle fibers over the 10-day period did not seem to make them any stronger, it did cause them all to grow in the same direction.
“Furthermore, we were excited to find that, when we triggered muscle contraction, aligned muscle was beating synchronously, whereas non-aligned muscle was not beating rhythmically,” said Raman. “This confirmed our understanding that the form and function of muscle are intrinsically connected, and that controlling form can help us control function.”
Raman and colleagues plan to take the study further by investigating how different mechanical stimulation regimens impact both healthy and diseased muscle fibers. Additionally, they plan to study how mechanical stimulation affects other types of cells.