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Published37 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Alex Homer & Navtej JohalBBC Shared Data Unit & BBC NewsThe UK government is behind the curve in tracking the spread of new super-strength drugs, a doctor who has treated patients has said. More than 100 deaths have now been linked to synthetic opioids called nitazenes since the summer, according to the National Crime Agency. Dr Mark Pucci says flawed data collection methods mean the numbers are a significant underestimate.On Wednesday, fifteen synthetic opioids became Class A drugs.Under the Misuse of Drugs Act, those caught in their supply and production could face up to life in prison, the Home Office said, while those caught in possession could face up to seven years.Home Secretary James Cleverly said: “Placing these toxic drugs under the strictest controls sends a clear message that the consequences for peddling them will be severe.”The drugs are stronger than heroin and fentanyl, a prolific killer in the US.Two people recovering from heroin addictions told the BBC how they nearly died after accidentally taking the new drugs.Warning: This article contains descriptions of drugs useThe National Crime Agency (NCA) believes nitazenes are produced in illicit labs in China and brought into the UK through the Royal Mail and other parcel operators.In the UK, they are mostly mixed with heroin by organised gangs.They have also been found in samples of illegal diazepam tablets, most likely bought online.Fourth wave of fentanyl crisis hits every corner of USWarning over potential risk of synthetic opioidsDrugs stronger than heroin linked to 54 UK deathsExperts say the authorities have not acted fast enough to track non-fatal overdoses involving nitazenes.They say tracking overdose data can show where the drugs have spread and therefore predict and prevent deaths. But currently, there is no national system. Overdose figures are gathered by government from local services and are based on tests of seized drugs or samples from other users believed to have bought from the same batch.Those records, obtained through a Freedom of Information request, suggest there were four non-fatal nitazene overdoses across the West Midlands in the last six months of 2023.Consultant in clinical toxicology Dr Mark Pucci, who works in Birmingham and Sandwell, believes those figures under-report the issue.He observed 13 patients who overdosed and survived between July and October 2023.They were among 19 people whose blood or urine contained the drugs. None of the patients knew beforehand they had taken them.Dr Pucci said: “I believe there are very few NHS labs around the country that are set up to test for nitazenes. “I do believe England is behind the curve on this matter and is now playing catch up. The data collection method they are using in terms of testing drug paraphernalia is only ever going to be the tip of the iceberg.”Most recent figures put the death toll linked to nitazenes across the UK at 101 people – seventy-six of them in England. At least a further 49 cases await further testing.BBC News spoke to Matt Perry, who has been receiving help with addiction from the charity Change Grow Live for 16 years.He previously spent up to £1,000 a day on heroin and crack cocaine which he funded through crime.When Matt bought what he thought was heroin last August, he could “feel himself going over [overdosing]” and called 999 for help.He woke up in hospital with a tube down his throat, a catheter fitted and wearing a heart monitor.”It scared the daylights out of me,” he said.He had flatlined on the way to hospital and was technically dead for seconds before shocks from a defibrillator brought him back. “I was in hospital for five days and it was the worst feeling I’ve ever had,” he said.He now has tissue damage in his brain and has suffered pain around his kidneys for the past six months. Tests of some leftover drugs proved the link to nitazenes.The experience has encouraged Matt, aged 35, to stay off drugs and he is back in work as a plant operator. “I have taken so much out of the community on my journey and I want to give something back.”Nitazenes are not going to be stopped until we get this word out. People are going to die.”Sarah, not her real name, has been taking heroin since the age of 15 and is now 43.She took nitazenes unwittingly last summer when she bought some bags from her regular dealer. Sarah, who was taking up to 10 bags of heroin a day, later found out someone she knew who bought from the same batch of drugs had overdosed and died.She has not taken heroin since.”It’s been four or five months and I still feel ill,” she said. “The withdrawal makes you feel suicidal. You can’t move off the bed. “They need to stop it from coming in to the country.”Dr Judith Yates, who collates data about drug deaths in Birmingham, said advice to government to track drugs spread by focussing more on non-fatal overdoses had not been followed. She said: “People seem to think it is OK to share information in darkened rooms, but are frightened of telling those people whose lives are at risk.”The European Monitoring Centre for Drugs and Drug Addiction told the BBC tracking non-fatal overdoses was “definitely one of the key data to consider”.One reason thought to be behind the emergence of nitazenes is the ban of harvesting opium poppies in Afghanistan.Charles Yates, the National Crime Agency’s deputy director, says while there are “significant reserves” of heroin in the UK, the purity at street-level has continued to decline long-term.The number of deaths involving nitazenes was “likely… under-represented”, in part due to “information gaps” within the UK drugs market, he added.All areas had forensic testing facilities, but nitazenes remained hard to identify because of their novelty, he said.Charlie Mack is the chief executive of the charity Cranstoun, which works with young people with drug problems. He has called for a co-ordinated, national response.He said: “We fear that now that these types of drugs are in the UK, it will only continue and become more prevalent. “We only need to look to the US where synthetic opioids are one of the biggest killers of under 50s. We cannot let that happen here.”The Department of Health and Social Care said it had a surveillance system about new trends in the drugs market, and it hoped to add more information from ambulance call-outs and hospital admissions.It is consulting on a legal change so more professionals can give out take-home supplies of naloxone – a medicine that reverses the effects of opioid overdose.It also hopes to harness new technology to prevent drug deaths, with 12 projects awarded a share of £5m funding to develop ideas.The government says it is highly alert to the threat of synthetic opioids and has set up a taskforce to co-ordinate its response.Additional data journalism: Paul BradshawIf you have been affected by the issues raised in this story help and support is available via the BBC Action LineBBC News agreed not to use Sarah’s real nameSign up for our morning newsletter and get BBC News in your inbox.More on this storyDrugs stronger than heroin linked to 54 UK deathsPublished11 December 2023’We had to investigate our autistic son’s death’Published4 January’People will keep dying’: Fentanyl crisis grips Mexico’s border citiesPublished7 FebruaryEasy access to online drugs fed mum’s addictionPublished29 July 2022

Can an experimental drug cure opioid addiction? Andrew Jacobs, who writes about psychedelic medicine for The Times, explored the “promise and peril” of ibogaine.Times Insider explains who we are and what we do and delivers behind-the-scenes insights into how our journalism comes together.As a reporter covering psychedelic medicine for the Health and Science desk at The New York Times, the drugs that often command my attention are familiar to any veteran psychonaut: ketamine; LSD; psilocybin, or “magic mushrooms”; and MDMA, also known as Molly or Ecstasy.Many of these psychoactive substances have been the subjects of research for years, if not decades. And a growing tranche of scientific evidence suggests these drugs have the potential to treat some mental health issues, among them depression, substance abuse and eating disorders.But research on psychedelics has largely ignored ibogaine, a drug that’s derived from a plant native to the rainforests of Central Africa.Over the past three years on this beat, I have interviewed researchers who have occasionally mentioned ibogaine, often in tones that hinted at both promise and peril. The handful of experts who have worked directly with the drug cast it as a powerful addiction interrupter — one that can quell the excruciating symptoms of opioid withdrawal and tame the cravings to use again. According to a number of small studies, many patients report being able to achieve long-term sobriety after a single therapeutic session. (In the United States, the drug remains illegal; many patients will travel abroad for ibogaine therapy.)But there are downsides. An ibogaine journey can be grueling. Some patients can feel the effects for up to 24 hours.From 1990 to 2020, more than 30 ibogaine-related deaths have also been reported — some of them ascribed to severe arrhythmia, or an irregular heartbeat, that in rare cases can lead to fatal cardiac arrest. Those risks were enough to prompt the Food and Drug Administration in the 1990s to end further study on ibogaine’s potential to treat crack cocaine addiction.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.

Published16 minutes agoShareclose panelShare pageCopy linkAbout sharingBy Emma BarnettPresenter, Woman’s HourSometimes things come along that you didn’t know you needed until you are offered them. That is how I feel about the government’s new baby loss certificates. Last month, I came off air after presenting Woman’s Hour, went straight online and headed to a government website. I was prompted to do so by an emotional interview I had conducted about this new initiative with Zoe Clark-Coates, founder of the baby loss charity, Mariposa Trust. She has been tirelessly campaigning for nine years, based on her own extremely painful experiences.During our conversation, it suddenly dawned on me – I too could apply for this certificate, which had come about as part of the government’s Pregnancy Loss Review. I didn’t give it any more thought. I just knew instinctively that I wanted to, becoming part of the first wave of women in England to apply.I messaged my husband to explain what I was planning to do and asked if he was comfortable with it. I was going to put his name down and I didn’t want him to receive an email asking for his consent without prior warning. He was. You don’t need access to your medical notes. Nor is the process limited to one baby loss. Filling in the form only took a matter of minutes but it was far more emotional than I had anticipated. One of the questions you are asked is when you lost your baby, and I realised I didn’t actually know what month or even year – despite it happening not that long ago, in January 2022.That whole period had become a grief-infused blur. A time where days and dates mattered little. Cue having to scroll back through old messages to family and friends where I had broken the news.Re-reading the words I had chosen to communicate this news was tough, because it catapulted me back into that stark place. But I could also see, in the way I had decided to tell all of our nearest and dearest, that even then, in the fog of misery, I was trying to make what had happened seem real, important and proper.We lost our baby in January 2022. Naively I had hoped you couldn’t lose a baby that had taken five rounds of IVF to create. I somehow thought the gruelling process to arrive at this much-longed for outcome would magically inoculate me against the frightening reality that one in four pregnancies end in loss. It couldn’t and didn’t.I was alone when I found out – not something I recommend if you can help it. I hadn’t been feeling quite right for a few days and wanted some reassurance. So I booked a private scan, to the tune of £120, to put my mind at ease. My husband had offered to come but it was tricky with his work that day, so I told him not to worry, I would do it alone.That turned out to be a big mistake. I stumbled out of the clinic, into the harsh sunlight of a busy London road, knowing that our dream was over. Gone.Weirdly, I can remember I was meant to be cooking a roast chicken that night. It never got made. Time was now starkly divided between before that moment in the sonographer’s room, where the sound of only one heartbeat filled my ears – my own – and after.Living in the after was grim and tearful.I suppose it is to the testament of the living, and those who surround you in love in the days and weeks afterwards, that they so badly want you to move on and not lose hope, and possibly start trying again.But I didn’t want to move on. Not for a long while. I had formed a relationship with our baby, daring to map out a little of our future together. But beyond medical forms, conversations with my stunned and deeply saddened husband, my texts to people about our loss and my memories of such a bond, there was nothing else to show the whole episode happened.Like millions of women before me, the baby lived within me and died within me. My body and mind were the keeper and witness. What are baby loss certificates?From February 2024, people in England who have lost a baby before 24 weeks of pregnancy have been able to apply for a certificate in memory of their babyYou must be at least 16 years old and your pregnancy ended on or after 1 September 2018You do not need to provide any medical proof, so can still apply if your loss was not recorded by a medical team or doctor The certificate is optional and, while official, is not a legal document Currently you can only apply if you live in England and were residing in the country at the time of your lossIn Scotland, you can apply for an entry to be made in the Memorial Book and a commemorative certificate is issued free of charge. The Welsh and Northern Ireland governments are working with counterparts in England to explore introducing baby loss certificatesMany people will not need a piece of paper. But the moment I realised I would like to have one was when Zoe and I spoke about having something official for the family file. Our loss is part of our family story and now there can be a piece of official paperwork to document it.Women and our stories are missing from many historical records because for so long we simply weren’t deemed worthy of properly recording. Our gains, losses and even our names lived and died with us. There are huge holes in people’s family trees because women were simply not properly documented.I even felt the act of applying for a baby loss certificate to be a political one – a refusal that something so major in our family’s life be erased and not known about. And when it arrived, 10 days later, in its crisp envelope and printed on thick white paper complete with an official government masthead – I felt weirdly satisfied, almost vindicated. It happened.Here was some physical proof and something external to me which my husband and our children – when they are older – could read as part of the story of our lives, alongside our marriage certificate, birth certificates and all the other paraphernalia that documents our existences. I don’t wish to speak for my husband, but I will say with his permission, that he felt it was a hugely positive thing to do too, and offered a touch point for him about something that was very bound up with me and my body.I think these certificates could also make people’s grief more accessible to others, as well as offering something more official to mark all that a pregnancy can mean and help memorialise it too.They will not be for everyone. Nor will they be all someone needs to pay tribute to the memory of their loss. And yet demand is expected to be high – so high the government has limited who can apply in England to those who suffered losses from 2018 onwards.This is a temporary time limitation to avoid the system becoming overwhelmed. In time it will open to all, and many women have been in touch with us at Woman’s Hour to say they will be applying to mark losses that happened decades ago.Our certificate has now been filed in the folder alongside the birth certificates of our other children. I expect I will sometimes reach for it in quiet moments and reflect some more. I do that already without any paperwork, but I also do like knowing that it’s there, recorded, like the very real and harrowing experience it was.Emma will be talking about her experience on Woman’s Hour on Wednesday 20 March at 10:00 GMT on BBC Radio 4.If you are affected by any of the issues raised in this story, support and advice is available via the BBC Action Line.More on this storyBaby loss certificates introduced in EnglandPublished22 February

Published10 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Michelle RobertsDigital health editorScientists say they have successfully eliminated HIV from infected cells, using Nobel Prize-winning Crispr gene-editing technology. Working like scissors, but at the molecular level, it cuts DNA so “bad” bits can be removed or inactivated.The hope is to ultimately be able to rid the body entirely of the virus, although much more work is needed to check it would be safe and effective. Existing HIV medicines can stop the virus but not eliminate it. The University of Amsterdam team, presenting a synopsis, or abstract, of their early findings at a medical conference this week, stress their work remains merely “proof of concept” and will not become a cure for HIV any time soon.And Dr James Dixon, stem-cell and gene-therapy technologies associate professor at the University of Nottingham, agrees, saying the full findings still require scrutiny.”Much more work will be needed to demonstrate results in these cell assays can happen in an entire body for a future therapy,” he said.”There will be much more development needed before this could have impact on those with HIV.”‘Extremely challenging’Other scientists are also trying to use Crispr against HIV. And Excision BioTherapeutics says after 48 weeks, three volunteers with HIV have no serious side effects.But Dr Jonathan Stoye, a virus expert at the Francis Crick Institute, in London, said removing HIV from all the cells that might harbour it in the body was “extremely challenging”. “Off-target effects of the treatment, with possible long-term side effects, remain a concern,” he said.”It therefore seems likely that many years will elapse before any such Crispr-based therapy becomes routine – even assuming that it can be shown to be effective.” HIV infects and attacks immune-system cells, using their own machinery to make copies of itself.Even with effective treatment, some go into a resting, or latent, state – so they still contain the DNA, or genetic material, of HIV, even if not actively producing new virus.Most people with HIV need life-long antiretroviral therapy. If they stop taking these drugs, the dormant virus can reawaken and cause problems again.A rare few have been apparently “cured”, after aggressive cancer therapy wiped out some of their infected cells, but this would never be recommended purely to treat HIV. More on this storyRare case of woman’s body ridding itself of HIVPublished16 November 2021Second patient cured of HIV, say doctorsPublished10 March 2020

Vapes have often been heralded as a “safer” way to consume either nicotine or cannabis, where legal to do so. But the devices present their own suite of risks that are slowly being revealed as they undergo increasing research and regulation. Now, researchers have discovered that nano-sized toxic metal particles may be present in cannabis vaping liquids even before the vaping device is heated, and the effect is worse in unregulated products.
The researchers will present their results today at the spring meeting of the American Chemical Society (ACS). ACS Spring 2024 is a hybrid meeting being held virtually and in person March 17-21; it features nearly 12,000 presentations on a range of science topics.
While cannabis regulation and legalization are still growing in the U.S., it was made federally legal in Canada under its Cannabis Act in 2018. “Cannabis vapes are newly regulated products in Canada, so we don’t yet have much scientific data about them,” says Andrew Waye, who will present the work at the meeting. “This is an opportunity for us to look at some of the questions concerning the risks and unknowns of cannabis vapes.” Waye manages the research program at the Office of Cannabis Science and Surveillance at Health Canada.
Unlike smoking, vaping does not involve a combustion reaction, which produces harmful byproducts. Instead, a vaping device heats a liquid until it evaporates into an inhalable vapor. As a result, it is often seen as a safer method to consume cannabis or nicotine. But research on nicotine vapes has shown that the metal components that heat the vape liquid may release harmful elemental metals, including nickel, chromium and lead, which can then be transported into the aerosol and deposited into the user’s body.
Waye’s team wanted to investigate whether this was also true for cannabis vapes. To do so, the group collaborated with Zuzana Gajdosechova, who is a scientist at the Metrology Research Centre of the National Research Council of Canada, which has been involved in cannabis testing and standardization for several years.
The team gathered 41 samples of cannabis vape liquids — 20 legal, regulated samples from the Ontario Cannabis Store and 21 samples from the illicit market provided by the Ontario Provincial Police. The liquids were analyzed by mass spectrometry to look for the presence of 12 metals. Regulated cannabis products are routinely tested for some of the analyzed metals, as well as other contaminants.
To verify the team’s findings, Gajdosechova collaborated with imaging experts and used techniques such as scanning electron microscopy to provide a visual confirmation of the metal particles. While some metals, such as arsenic, mercury and cadmium, were within the generally accepted tolerance limits for cannabis products, others were detected in concentrations considered to be very high. The most striking example proved to be lead: Some unregulated samples contained 100 times more lead than the regulated samples, far exceeding the generally accepted tolerance limit.

Importantly, this metal contamination was found in the liquid of cannabis vapes that had never been used and were less than six months old. “The evidence strongly suggests that metal contamination can come from the device when it’s produced, and not from the heating of the coils,” explains Gajdosechova. “But depending on the quality of the device, the contamination may be increased by that heating.”
Additionally, the team found that vapes belonging to the same production lot could contain different levels of metal contamination, demonstrating a high level of variability between samples. This could have implications for testing procedures, as Canadian regulations require samples to be representative of the whole lot or batch and that testing be done at or after the last step where contamination can occur. “If contamination is happening when the device is assembled, you should be testing at that stage rather than earlier,” says Waye.
Next, the team wanted to investigate the size of the metal particles to understand their potential health risks. Using single particle inductively coupled plasma mass spectrometry, the researchers found many particles that were of nanoscale size. “Some nano-sized metal particles are highly reactive and potentially harmful,” says Gajdosechova.
Moving forward, the team wants to determine how many of these particles are transmitted into the vape aerosol when a device is used. This is when the metals could get into users’ lungs, which will be important to determine the public health implications of these findings. The effect has been demonstrated in nicotine vapes, and the researchers expect that cannabis vapes could show the same.
“Different types of cannabis products present different risks. Our research doesn’t answer whether vaping is riskier than smoking, it just underlines that the risks may be different. Previously uncharacterized risks with cannabis vaping are still being identified,” concludes Waye. So, while there isn’t necessarily one way to “safely” consume these products, this research demonstrates that regulation can help create safer cannabis products overall.
This research was funded by Health Canada.

The brain is an incredibly complex and active organ that uses electricity and chemicals to transmit and receive signals between its sub-regions.
Researchers have explored various technologies to directly or indirectly measure these signals to learn more about the brain. Functional magnetic resonance imaging (fMRI), for example, allows them to detect brain activity via changes related to blood flow.
Yen-Yu Ian Shih, PhD, professor of neurology and associate director of UNC’s Biomedical Research Imaging Center, and his fellow lab members have long been curious about how neurochemicals in the brain regulate and influence neural activity, blood flow, and subsequently, fMRI measurement in the brain. A new study by the lab has confirmed their suspicions that fMRI interpretation is not as straightforward as it seems.
“Neurochemical signaling to blood vessels is less frequently considered when interpreting fMRI data,” said Shih, who also leads the Center for Animal MRI. “In our study on rodent models, we showed that neurochemicals, aside from their well-known signaling actions to typical brain cells, also signal to blood vessels, and this could have significant contributions to fMRI measurements.”
Their findings, published in Nature Communications, stem from a $3.8-million grant from the National Institutes of Health and UNC’s investments in supporting the installation and upgrade of two 9.4-Tesla animal MRI systems and a 7-Tesla human MRI system at the Biomedical Research Imaging Center.
When activity in neurons increases in a specific brain region, blood flow and oxygen levels increase in the area, usually proportionate to the strength of neural activity. Researchers decided to use this phenomenon to their advantage and eventually developed fMRI techniques to detect these changes in the brain.
For years, this method has helped researchers better understand brain function and influenced their knowledge about human cognition and behavior. The new study from Shih’s lab, however, demonstrates that this well-established neuro-vascular relationship does not apply across the entire brain because cell types and neurochemicals vary across brain areas.

Shih’s team focused on the striatum, a region deep in the brain involved in cognition, motivation, reward, and sensorimotor function, to identify the ways in which certain neurochemicals and cell types in the brain region may be influencing fMRI signals.
For their study, Shih’s lab controlled neural activity in rodent brains using a light-based technique, while measuring electrical, optical, chemical, and vascular signals to help interpret fMRI data. The researchers then manipulated the brain’s chemical signaling by injecting different drugs into the brain and evaluated how the drugs influenced the fMRI responses.
They found that in some cases, neural activity in the striatum went up, but the blood vessels constricted, causing negative fMRI signals. This is related to internal opioid signaling in the striatum. Conversely, when another neurochemical, dopamine, predominated signaling in striatum, the fMRI signals were positive.
“We identified several instances where fMRI signals in the striatum can look quite different from expected,” said Shih. “It’s important to be mindful of underlying neurochemical signaling that can influence blood vessels or perivascular cells in parallel, potentially overshadowing the fMRI signal changes triggered by neural activity.”
Members of Shih’s lab, including first- and co-authors Dominic Cerri, PhD, and Lindsey Walton, PhD, travelled to the University of Sussex in the United Kingdom, where they were able to perform experiments and further demonstrate the opioid’s vascular effects.
They also collected human fMRI data at UNC’s 7-Tesla MRI system and collaborated with researchers at Stanford University to explore possible findings using transcranial magnetic stimulation, a procedure that uses magnetic fields to stimulate the human brain.
By better understanding fMRI signaling, basic science researchers and physician scientists will be able to provide more precise insights into neural activity changes in healthy brains, as well as in cases of neurological and neuropsychiatric disorders.
The research was supported by Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative grant RF1MH117053 and High-End Instrumentation grants S10OD026796 and S10MH124745from the National Institutes of Health.

A research team led by the University of California, Irvine has discovered the key role that the APOBEC3A and APOBEC3B enzymes play in driving cancer mutations by modifying the DNA in tumor genomes, offering potential new targets for intervention strategies.
The study, published today online in the journal Nature Communications, describes how the researchers identified the process by which APOBEC3A and APOBEC3B detect specific DNA structures, resulting in mutations at distinct positions within the tumor genome.
“It’s critical to understand how cancer cells accumulate mutations leading to hot spots that contribute to disease progression, drug resistance and metastasis,” said corresponding author Rémi Buisson, UCI assistant professor of biological chemistry. “Both APOBEC3A and APOBEC3B were known to generate mutations in many kinds of tumors, but until now we did not know how to identify the specific type caused by each. This finding will allow us to develop novel therapies to suppress mutation formation by directly targeting each enzyme accordingly.”
In this study, graduate student Ambrocio Sanchez and postdoctoral fellow Pedro Ortega, both in Buisson’s laboratory at the UCI School of Medicine, developed a new method to characterize the particular kind of DNA modified by APOBEC3A and APOBEC3B. It revealed that the two enzymes do not recognize the same DNA sequences and structures within the genomes of cancer cells. Based on this observation, an innovative approach utilizing these unique target preferences was employed to classify cancer patients who had accumulated mutations caused by each enzyme.
“The next steps are to investigate whether mutations caused by these enzymes lead to various types of therapy resistance. It’s also critical to identify molecules that inhibit APOBEC3A and APOBEC3B to prevent mutations from forming. Our findings could, in the future, help to assess patient risk before treatment and suppress tumor evolution using the appropriate drug therapy,” Buisson said.
Other team members included undergraduate and graduate students and postdoctoral fellows from UCI, Harvard Medical School, the University of Southern California, the University of Texas at San Antonio and the University of Minnesota.
This work was supported by the National Institutes of Health’s Research Supplements to Promote Diversity in Health-Related Research program under award R37-CA252081-S; California Institute for Regenerative Medicine stem cell biology training grant TG2-01152; European Molecular Biology Organization postdoctoral fellowship ALTF 213-2023; Cancer Prevention and Research Institute of Texas research training award RP 170345 and Recruitment of Established Investigators award CPRIT RR220053; the National Cancer Institute under awards R37-VA252081 and P01-CA234228; the National Institute of Allergy and Infectious Diseases under award R01 AI150524; and access to UCI’s Genomics Research and Technology Hub, affiliated with the Chao Family Comprehensive Cancer Center, under grant P30-CA062203.

A new study in people undergoing surgery to treat seizures related to epilepsy shows that pauses in speech reveal information about how people’s brains plan and produce speech.
Led by researchers at NYU Grossman School of Medicine, the study results add to evidence that neighboring brain regions, the inferior frontal gyrus and the motor cortex, play an important role in such planning before words are said aloud. Both are part of the folded top layers of the brain, or cerebral cortex, which has long been known to control the muscle (motor) movements in the throat and mouth needed to produce speech. Less clear until now was how closely these regions determine the mix of sounds and words people want to say aloud, the authors report.
Publishing in the journal Brain online March 19, the findings come from an analysis of hundreds of brain-mapping recordings made on 16 patients between the ages of 14 and 43 preparing for surgery to treat epilepsy at NYU Langone Health between 2018 and 2021.
As a routine part of their procedures, surgeons electrically (and painlessly) stimulate specific parts of the brain while asking patients to perform standardized speaking tasks. Patients are asked, for example, to recite numbers or days of the week, or even the Pledge of Allegiance. The goal before surgery, researchers say, is to isolate and spare the parts of the brain nearby needed for speech, as marked by increased slurring or total loss of speech following electrical stimulation. This enables surgeons to remove only the brain tissue responsible for the errant electrical signals that cause seizures.
What makes the new study unique, the researchers say, was their measurement and analysis of the time intervals, lasting less than two seconds, during which brain stimulation starts and speech becomes slurred and eventually stops. Previous research, they note, did not directly measure such latencies, but instead relied on behavioral observations to inform which brain regions were involved in whether a patient could continue to speak or not after stimulation of the cortex.
Measuring the latencies, they say, provides new insight into the parts of the cortex involved in planning speech, even if not responsible for actually voicing and mouthing the words. Among the new study findings was that latencies between electrical stimulation and eventual loss of the ability to speak were different among brain regions.
Latencies were longest in the inferior or lower regions of the motor cortex as well as another surface layer, the inferior frontal gyrus, at 1.0 second and 0.75 second, respectively. Because patients were able to keep speaking so long after stimulation, investigators say this suggests that these regions are more likely than other regions to be involved in planning what people want to say.

Smaller latencies, lasting on average 0.5 second, were found in other parts of the motor cortex. Researchers say these shorter interruptions of speech indicate that these regions play a more crucial role in the physical mechanics of speaking.
Based on these observations, researchers determined that a pattern of longer latencies corresponded to speech planning in different regions of the brain cortex more likely than shorter latencies, which corresponded to parts of the brain cortex involved in speech production.
“Our study adds evidence for the role of the brain’s motor cortex and inferior frontal gyrus in planning speech and determining what people are preparing to say, not just voicing words using the vocal cords or mouthing the words by moving the tongue and lips,” said study lead investigator Heather Kabakoff, PhD, a speech pathologist at NYU Langone.
“Our results show that mapping out the millisecond time intervals, or latencies, between electrical stimulation in parts of the brain to the disruption or slurring of words and eventual inability to speak can be used to better understand how the human brain works and the roles played by different brain regions in human speech,” said study senior investigator and neuroscientist Adeen Flinker, PhD. “When it comes to mapping out functions of the brain cortex involved in speech, timing is key.”
Flinker, an associate professor in the Department of Neurology at NYU Langone, says the team’s overall findings also confirm that motor execution and speech planning occur in distinctly different areas of the brain.
Clinically, Flinker says the team findings, if further research confirms their work, could help surgeons better refine their brain mapping to protect patients’ speech.

Researchers say their next steps are to evaluate latency patterns in other parts of the brain to determine if they too play a role in the finer functions of planning speech or physically making sounds and words. Tasks include the naming of pictures aloud to determine if poststimulation latencies help distinguish parts of the brain needed to interpret visual inputs and process them into actual words.
They also want to investigate whether latency patterns can expose real-time speech feedback mechanisms by measuring how long it takes patients to correct forced errors. This, they say, could provide insight into how people use the sound of their own voice to control the way they sound.
Funding support for this research was provided by National Institutes of Health grants R01DC018805, R01NS109367, R01NS115929, and F32DC021094.
Besides Flinker and Kabakoff, other NYU Langone researchers involved in the study are co-investigators Leyao Yu, BA; Daniel Friedman, MD; Patricia Dugan, MD; Werner Doyle, MD; and Orrin Devinsky, MD.

Lyme disease, a bacterial infection transmitted by ticks, affects nearly half a million people in the United States every year. In most cases, antibiotics effectively clear the infection, but for some patients, symptoms linger for months or years.
Researchers at MIT and the University of Helsinki have now discovered that human sweat contains a protein that can protect against Lyme disease. They also found that about one-third of the population carries a genetic variant of this protein that is associated with Lyme disease in genome-wide association studies.
It’s unknown exactly how the protein inhibits the growth of the bacteria that cause Lyme disease, but the researchers hope to harness the protein’s protective abilities to create skin creams that could help prevent the disease, or to treat infections that don’t respond to antibiotics.
“This protein may provide some protection from Lyme disease, and we think there are real implications here for a preventative and possibly a therapeutic based on this protein,” says Michal Caspi Tal, a principal research scientist in MIT’s Department of Biological Engineering and one of the senior authors of the new study.
Hanna Ollila, a senior researcher at the Institute for Molecular Medicine at the University of Helsinki and a researcher at the Broad Institute of MIT and Harvard, is also a senior author of the paper, which appears today in Nature Communications. The paper’s lead author is Satu Strausz, a postdoc at the Institute for Molecular Medicine at the University of Helsinki.
A surprising link
Lyme disease is most often caused by a bacterium called Borrelia burgdorferi. In the United States, this bacterium is spread by ticks that are carried by mice, deer, and other animals. Symptoms include fever, headache, fatigue, and a distinctive bulls-eye rash.

Most patients receive doxycycline, an antibiotic that usually clears up the infection. In some patients, however, symptoms such as fatigue, memory problems, sleep disruption, and body aches can persist for months or years.
Tal and Ollila, who were postdocs together at Stanford University, began this study a few years ago in hopes of finding genetic markers of susceptibility to Lyme disease. To that end, they decided to run a genome-wide association study (GWAS) on a Finnish dataset that contains genome sequences for 410,000 people, along with detailed information on their medical histories.
This dataset includes about 7,000 people who had been diagnosed with Lyme disease, allowing the researchers to look for genetic variants that were more frequently found in people who had had Lyme disease, compared with those who hadn’t.
This analysis revealed three hits, including two found in immune molecules that had been previously linked with Lyme disease. However, their third hit was a complete surprise — a secretoglobin called SCGB1D2.
Secretoglobins are a family of proteins found in tissues that line the lungs and other organs, where they play a role in immune responses to infection. The researchers discovered that this particular secretoglobin is produced primarily by cells in the sweat glands.
To find out how this protein might influence Lyme disease, the researchers created normal and mutated versions of SCGB1D2 and exposed them to Borrelia burgdorferi grown in the lab. They found that the normal version of the protein significantly inhibited the growth of Borrelia burgdorferi. However, when they exposed bacteria to the mutated version, twice as much protein was required to suppress bacterial growth.

The researchers then exposed bacteria to either the normal or mutated variant of SCGB1D2 and injected them into mice. Mice injected with the bacteria exposed to the mutant protein became infected with Lyme disease, but mice injected with bacteria exposed to the normal version of SCGB1D2 did not.
“In the paper we show they stayed healthy until day 10, but we followed the mice for over a month, and they never got infected. This wasn’t a delay, this was a full stop. That was really exciting,” Tal says.
Preventing infection
After the MIT and University of Helsinki researchers posted their initial findings on a preprint server, researchers in Estonia replicated the results of the genome-wide association study, using data from the Estonian Biobank. These data, from about 210,000 people, including 18,000 with Lyme disease, were later added to the final Nature Communications study.
The researchers aren’t sure yet how SCGB1D2 inhibits bacterial growth, or why the variant is less effective. However, they did find that the variant causes a shift from the amino acid proline to leucine, which may interfere with the formation of a helix found in the normal version.
They now plan to investigate whether applying the protein to the skin of mice, which do not naturally produce SCGB1D2, could prevent them from being infected by Borrelia burgdorferi. They also plan to explore the protein’s potential as a treatment for infections that don’t respond to antibiotics.
“We have fantastic antibiotics that work for 90 percent of people, but in the 40 years we’ve known about Lyme disease, we have not budged that,” Tal says. “Ten percent of people don’t recover after having antibiotics, and there’s no treatment for them.”
The researchers note that people who have the protective version of SCGB1D2 can still develop Lyme disease, and they should not assume that they won’t. One factor that may play a role is whether the person happens to be sweating when they’re bitten by a tick carrying Borrelia burgdorferi.
SCGB1D2 is just one of 11 secretoglobin proteins produced by the human body, and Tal also plans to study what some of those other secretoglobins may be doing in the body, especially in the lungs, where many of them are found.
“The thing I’m most excited about is this idea that secretoglobins might be a class of antimicrobial proteins that we haven’t thought about. As immunologists, we talk nonstop about immunoglobulins, but I had never heard of a secretoglobin before this popped up in our GWAS study. This is why it’s so fun for me now. I want to know what they all do,” she says.

The middle-aged brain could provide a window into future cognitive health, researchers write in a review publishing March 19 in the journal Trends in Neurosciences. The team reviewed evidence from human and animal studies suggesting that middle age — commonly considered as the period between 40 and 60 or 65 years of age — marks a shift in brain aging. They argue that more research should be dedicated to middle age, a period of life that is historically understudied.
“Middle age is associated with specific and modifiable risk factors for future dementia risk,” write the authors, who include neuroscientist Yvonne Nolan of APC Microbiome Ireland at University College Cork. “We encourage giving this previously understudied period of life renewed consideration.”
Most studies of brain health and cognitive decline focus on older age groups, but by this time, interventions may have limited efficacy. Screening for risk of future cognitive decline could help by allowing treatment to begin earlier when it might be more effective. A better understanding of brain shifts during middle age might also help identify novel targets for therapy, the researchers say.
During middle age, the brain undergoes significant molecular, cellular, and structural changes, and many of these changes have been linked to cognitive decline, which has also been shown to accelerate during middle age.
“There is good evidence to suggest that the human brain undergoes non-linear structural and functional changes during middle age that have implications for cognitive functioning, and variation in these processes could account for individual trajectories in cognitive aging,” the authors write.
Structurally, middle age is associated with changes in the volume of several brain structures, shrinking of the hippocampus (a brain structure involved in memory and learning), and decreased connectivity between different parts of the brain.
“The fourth and fifth decades of life may be a turning point in the organization of brain networks, characterized by optimal efficiency, system segregation, and modularity, followed by accelerated decay of these properties,” the authors write.

Middle age is also associated with changes in gene expression, both within the brain and in other parts of the body. In the human brain, studies show increased expression of immune-related genes and decreased expression of synaptic genes. The authors also point to evidence suggesting that changes in other parts of the body may predict brain health and function.
“Factors in systemic circulation — mainly proteins secreted by various organs — are understood to mediate brain aging in terms of cognition, plasticity, adult neurogenesis, and neuroinflammation,” the authors write. “Some of the largest peaks of change across the entire adult lifespan occur during middle age, as measured in plasma, peripheral blood monocytes, and muscle.”
There is some evidence that exercise might aid healthy cognitive aging, but more research is needed. “Studying the intersection of aging- and exercise-related molecular processes could unveil new therapeutic targets,” the authors write.
Further research is also needed to investigate observed sex differences in brain aging, as evident in the higher rate of dementia in women, the researchers say. They also note that it will be important for future studies to differentiate processes that cause declining brain health from biomarkers that reflect compensatory mechanisms.
“Ultimately, scientists will want to find novel therapeutic targets to mitigate unhealthy cognitive aging,” the authors write. “We argue that applying recent trends in aging research to this period of life could reveal novel biomarkers and possible interventions to combat cognitive decline in an increasingly older global population.”
This research was supported by the Science Foundation Ireland, the Irish Health Research Board, and Alzheimer Nederland.