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Stroke is a leading cause of long-term disability worldwide. Each year more than 15 million people worldwide have strokes, and three-quarters of stroke survivors will experience impairment, weakness and paralysis in their arms and hands.
Many stroke survivors rely on their stronger arm to complete daily tasks, from carrying groceries to combing their hair, even when the weaker arm has the potential to improve. Breaking this habit, known as “arm nonuse” or “learned nonuse,” can improve strength and prevent injury.
But, determining how much a patient is using their weaker arm outside of the clinic is challenging. In a classic case of observer’s paradox, the measurement has to be covert for the patient to behave spontaneously.
Now, USC researchers have developed a novel robotic system for collecting precise data on how people recovering from stroke use their arms spontaneously. The first-of-its-kind method is outlined in a paper published in the November 15 issue of Science Robotics.
Using a robotic arm to track 3D spatial information, and machine learning techniques to process the data, the method generates an “arm nonuse” metric, which could help clinicians accurately assess a patient’s rehabilitation progress. A socially assistive robot (SAR) provides instructions and encouragement throughout the challenge.
“Ultimately, we are trying to assess how much someone’s performance in physical therapy transfers into real life,” said Nathan Dennler, the paper’s lead author and a computer science doctoral student.
The research involved combined efforts from researchers in USC’s Thomas Lord Department of Computer Science and the Division of Biokinesiology and Physical Therapy. “This work brings together quantitative user-performance data collected using a robot arm, while also motivating the user to provide a representative performance thanks to a socially assistive robot,” said Maja Matari?, study co-author and Chan Soon-Shiong Chair and Distinguished Professor of Computer Science, Neuroscience, and Pediatrics. “This novel combination can serve as a more accurate and more motivating process for stroke patient assessment.”
Additional authors are Stefanos Nikolaidis, an assistant professor of computer science; Amelia Cain, an assistant professor of clinical physical therapy, Carolee J. Winstein, a professor emeritus and an adjunct professor in the Neuroscience Graduate Program, and computer science students Erica De Guzmann and Claudia Chiu.

Mirroring everyday use
For the study, the research team recruited 14 participants who were right-hand dominant before the stroke. The participant placed their hands on the device’s home position — a 3D-printed box with touch sensors.
A socially assistive robot (SAR) described the system’s mechanics and provided positive feedback, while the robot arm moved a button to different target locations in front of the participant (100 locations in total). The “reaching trial” begins when the button lights up, and the SAR cues the participant to move.
In the first phase, the participants were directed to reach for the button using whichever hand came naturally, mirroring everyday use. In the second phase, they were instructed to use the stroke-affected arm only, mirroring performance in physiotherapy or other clinical settings.
Using machine learning, the team analyzed three measurements to determine a metric for arm nonuse: arm use probability, time to reach, and successful reach. A noticeable difference in performance between the phases would suggest nonuse of the affected arm.
“The participants have a time limit to reach the button, so even though they know they’re being tested, they still have to react quickly,” said Dennler. “This way, we’re measuring gut reaction to the light turning on — which hand will you use on the spot?”
Safe and easy to use

In chronic stroke survivors, the researchers observed high variability in hand choice and in the time to reach targets in the workspace. The method was reliable across repeated sessions, and participants rated it as simple to use, with above-average user experience scores. All participants found the interaction to be safe and easy to use.
Crucially, the researchers found differences in arm use between participants, which could be used by healthcare professionals to more accurately track a patient’s stroke recovery.
“For example, one participant whose right side was more affected by their stroke exhibited lower use of their right arm specifically in areas higher on their right side, but maintained a high probability of using their right arm for lower areas on the same side,” said Dennler.
“Another participant exhibited more symmetric use but also compensated with their less-affected side slightly more often for higher-up points that were close to the mid-line.”
Participants felt that the system could be improved through personalization, which the team hopes to explore in future studies, in addition to incorporating other behavioral data such as facial expressions and different types of tasks.
As a physiotherapist, Cain said the technology addresses many issues encountered with traditional methods of assessment, which “require the patient not to know they’re being tested, and are based on the tester’s observation which can leave more room for error.”
“This type of technology could provide rich, objective information about a stroke survivor’s arm use to their rehabilitation therapist,” said Cain. “The therapist could then integrate this information into their clinical decision-making process and better tailor their interventions to address the patient’s areas of weakness and build upon areas of strength.”

A new biologic “patch” that is activated by a person’s natural motion could be the key to fixing herniated discs in people’s backs, according to researchers at the Perelman School of Medicine at the University of Pennsylvania and the CMC VA Medical Center (CMCVAMC). Combining years of work from many different projects, the “tension-activated repair patches” (TARPs) provide controlled release of an anti-inflammatory molecule called anakinra from microcapsules over time, which helped discs in a large animal model regain the tension they need to reverse herniation and prevent further degeneration. This pre-clinical research is detailed in a paper published today in Science Translational Medicine.
“Currently there is no curative treatment for disc herniation, and the best thing out there is just like sticking a plain rubber plug into a hole in a tire. It will stay for a while but it won’t make a great seal,” said co-senior author Robert Mauck, PhD, a professor in Orthopaedic Surgery and director of the McKay Laboratory for Orthopaedic Surgery Research at Penn and research career scientist and co-director of the Translational Musculoskeletal Research Center at the CMCVAMC. “The patch we’ve developed is like the plug plus glue, so you’re actually bonding the patch. And since biomechanical movement activates the patch and makes it seal more strongly, it’s like having your tire patch get stronger the more miles you put on it.”
Herniation in the spine occurs when one of the soft discs that sits between the vertebrae develops a split or a hole, and the soft interior squeezes through. This means that the discs lose their tension and are unable to cushion the spine as usual, causing pain. To continue the tire analogy, it’s as if a tire has gone flat and the car is riding on its rim.
So the Penn Medicine and CMCVAMC researchers have developed TARPs to not just plug the hole, but allow tension to build back up, and re-cushion the vertebrae. That goal has been particularly tough to achieve to this point.
“The disc is a very complex tissue, which is different from muscle and skin in that it cannot heal its own structure and, in fact, continues to degenerate over time once its structure is compromised,” said Ana Peredo, PhD, who completed this research during her doctoral studies in Bioengineering at the School of Engineering and Applied Sciences at Penn. “We set out to recover the disc’s mechanical integrity while simultaneously attenuating inflammation in order to prevent further tissue damage and retain as much tissue function as possible.” –
Key to the TARP is having the body’s natural mechanics work to activate the release of anti-inflammatory molecules from the microcapsules within the patch. While they would theoretically still work if a person lay totally still for months, the reality of the disc tissue environment is that movement is its natural state.
And because the patch makes it as if there was never a hole to begin with, its application could have significant effects on the prevention of worsening pain related to disc degeneration.

“This is designed to be an early intervention that may change the course of disease progression,” said co-senior author Harvey Smith, MD, an associate professor of Orthopaedic Surgery and attending physician at the CMCVAMC. “Currently there’s no treatment to mitigate recurring herniations that actually heal the disc. So we’re looking at a disease that is very common in younger, working-age people that, downstream, leads to severe disc disease and the need for spinal fusion. The more we can prevent that, the better.”
This new prospective treatment, which has human and potentially veterinary applications, builds upon many years of research in the McKay Lab and at Penn, at the Translational Musculoskeletal Research Laboratory at the CMCVAMC, and within the Institute for Medical Translation at the New Bolton Center, and leverages foundational technologies used by many of the same researchers on this project to create bio-synthetic discs and other mechanically-activated drug delivery systems. Some of these advances are now being commercialized by Mechano Therapeutics, LLC , which was co-founded by Mauck and other co-authors on the current paper, George Dodge, PhD, previously an adjunct associate professor of Orthopaedic Surgery and the current CEO of the start-up, and Daeyeon Lee, a Penn Engineering professor, and supported by the Penn Center for Innovation.
“I have been working with emerging non-fusion spine technologies for 20 years, with very few making it to human clinical trials and beyond,” said Thomas Schaer, VMD, a veterinary surgeon and Director of the Institute for Medical Translation, New Bolton Center, at the Penn School of Veterinary Medicine. “This team has been working together for 15 years, and I believe we are practicing a highly focused approach to research that has significant potential for a translational breakthrough across a broad spectrum of spine care, not just for human patients but possibly also for our furry dog friends.”
While this research was primarily “proof of principle,” moving this treatment closer to the clinic will require longer trials in large animal models, the team said.
“This study was incredibly promising but went for one month, so we want to test for a longer time because there are ways we can fine-tune this patch,” said co-lead author Sarah Gullbrand PhD, a research assistant professor of Orthopaedic Surgery at Penn and research health scientist at the CMCVAMC. “We only targeted one biologic pathway this time using something that was already approved by the FDA, but there are tons of other factors that are approved. In the future, we’re interested in not only reducing inflammation, but also preventing cell death and improving overall healing.”
The research was funded by the Department of Veterans’ Affairs Rehabilitation Research and Development Service (I21 RX003447, IK6 RX003416, IK2 RX003118) and the National Institutes of Health (R01 AR071340) and was supported by the Penn Center for Musculoskeletal Disorders (P30 AR069619).

With the rise of new drugs that can target the amyloid-beta plaques in the brain that are an early sign of Alzheimer’s disease, new ways are needed to determine whether memory loss and thinking problems are due to Alzheimer’s disease or another neurodegenerative disorder. A new study published in the November 15, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology, shows that shrinkage in the hippocampus area of the brain is associated with cognitive decline, even in people who don’t have amyloid plaques in the brain. The hippocampus plays a role in memory.
“These results suggest that neurodegenerative diseases other than Alzheimer’s are contributing to this decline, and measuring the hippocampus volume may help us evaluate these causes that are currently difficult to measure,” said study author Bernard J. Hanseeuw, MD, PhD, of Harvard Medical School in Boston. “This could help us better predict who would respond to these new drugs as well as people’s trajectories of cognitive decline.”
The study involved 128 people with an average age of 72 who had no thinking or memory problems at the start of the study. The participants had several types of brain scans throughout the study to measure the amount of amyloid plaques and tau tangles in their brains, as well as the volume of the hippocampus. The tau protein is another biomarker of Alzheimer’s disease. The participants also had yearly cognitive evaluations over an average of seven years of follow-up.
Faster shrinkage in the hippocampus was associated with faster cognitive decline. When researchers looked at all of the biomarkers, they found that hippocampus atrophy was associated with cognitive decline independently of amyloid and tau levels. Hippocampus shrinkage on its own accounted for 10% of the difference in cognitive decline.
“These results emphasize that dementia is a complex condition with many underlying causes and suggest that types of dementia other than Alzheimer’s disease may contribute to shrinkage in the hippocampus and cognitive decline,” Hanseeuw said.
A limitation of the study was that most participants were highly educated and white people, so the results may not apply to all people.
The study was supported by the National Institutes of Health, Belgian Fund for Scientific Research, Welbio and Queen Elizabeth Medical Foundation.

Older people are using cannabis more than ever. Here’s what to know about its potential medicinal benefits and side effects as we age.Seniors are one of the fastest-growing populations of cannabis users in the United States. While some older adults have used pot for decades, studies suggest that others are turning to the drug for the first time to help them sleep better, dampen pain or treat anxiety — especially when prescription drugs, which often come with unwanted side effects, don’t work as intended.In 2007, only about 0.4 percent of people age 65 and older in the United States had reported using cannabis in the past year, according to the National Survey on Drug Use and Health. That number rose to almost 3 percent by 2016. As of 2022, it was at more than 8 percent.Nancy Herring, 76, has been using cannabis recreationally for her entire adult life — she describes herself as “one of the hippies from the ’60s.” But it wasn’t until her husband was diagnosed with Parkinson’s disease and dementia two years ago that she began to wonder about pot’s medicinal use.During the course of his illness, her husband, now 79, had developed insomnia. Soon, neither of them was sleeping.Doctors prescribed pills to help him rest, but “nothing really worked,” she said. At one point, he reacted so negatively to a medicine he ended up in the hospital.Then they tried an indica strain from a dispensary near where they live in Clearwater, Fla. Now, after one gummy and a hit on a pipe, her husband “can sleep at night, which is a huge thing,” she said.Marijuana’s medicinal properties have not been well studied, particularly among older users, making it difficult for doctors to counsel their patients on the benefits and risks. Cannabis companies have rushed to fill the void, offering tips to older adults about doses or formulations and even creating products meant to appeal to them. Meanwhile, as more seniors experiment with cannabis, they are evangelizing to one another about its benefits, and sharing the problems they’ve encountered along the way.“People are just desperate,” said Dr. Aaron Greenstein, a geriatric psychiatrist in Denver. “They’re willing to try anything.”When his own grandmother became convinced that she was reliving the Holocaust during the later stages of her dementia, taking a dissolvable strip with a small amount of THC — the psychoactive component in marijuana — put an end to her flashbacks and helped her feel at peace.“I have had dozens of patients who tell me that it has cured their various ailments,” said Dr. Haley V. Solomon, a geriatric psychiatrist in San Diego who, along with Dr. Greenstein, has written about the promise and risks of seniors using cannabis. “I think that it’s really important to listen to them, to acknowledge that and then to study it further.”Older adults need to be aware of potential drug interactions, she added, and also consider how cannabis can affect cognition, coordination and balance.Carminetta Verner, 88, started a cannabis club in her Maryland retirement community. She recently used ChatGPT to produce an 89-page manual about medical cannabis for her members. Greg Kahn for The New York Times‘Medicine isn’t working.’Without a North Star guiding older adults on how to use cannabis, there is a grass-roots effort among some seniors to teach one another.Carminetta Verner, 88, has become the go-to source for cannabis information at her retirement community, the sprawling Leisure World complex in Montgomery County, Md., which houses about 8,000 older adults.In 2018, she founded a club devoted to educating residents about medical cannabis. The club’s membership, which has now grown to about 100 people, might be higher if it weren’t for the stigma still associated with the drug, Ms. Verner said.“There are a lot of people up here that are suffering and in pain, and medicine isn’t working for them,” she said.Damien Cornwell, the owner of a dispensary in Binghamton, N.Y., that opened in February, said his business has attracted customers who are “seeking relief they can’t find at doctor’s office.” They have ailments such as rheumatoid arthritis, anxiety and insomnia, he said.As more states legalize cannabis — it is now permitted for recreational use in more than 20 states and Washington, D.C., and for medical use in 38 states and D.C. — the number of seniors who turn to marijuana will only continue to grow, experts said. An October Gallup poll found that about two-thirds of adults 55 and older think the use of marijuana should be legal.Cannabis brands are courting seniors.Steve Hickerson, who lives in Laguna Woods, Calif., wants to sleep better.He used cannabis sublingual drops but said they didn’t help, so he’s trying gummies, “which seem to work much better.” In the past, he felt using mind-altering drugs was morally wrong — “I’m a Christian,” he explained — but now, he said, “I’m 79, things are different.” He is willing to explore products that have a medical use.Companies are capitalizing on the newfound interest. Earlier this year, Mr. Hickerson was bused to an event organized by Glass House, one of the biggest cannabis brands in the country, along with about 50 other people from his retirement community who were offered cannabis products at a substantial discount.The company Trulieve is also connecting with seniors. It has the largest retail footprint for cannabis products in the United States and a 750,000-square-foot cannabis cultivation facility in north Florida. Much like Glass House, Trulieve organizes “silver tours” that bring seniors to local dispensaries, among other opportunities for in-person education.Kim Rivers, the co-founder and chief executive of Trulieve, said their “wisdom” customers — those 55 and older — are growing year over year. In Florida, she added, these adults represent 20 percent of their customer base.Bristol Extracts, which manufactures cannabis in New York, has created a brand called Senior Moments — a collection of tinctures, gummies and mints that debuted in March.“IT’S TIME TO SPICE THINGS UP A LITTLE!” proclaims the company’s website. “Growing older doesn’t have to be mundane.”The brand’s edibles also have ingredients like ginkgo biloba that are advertised as supporting “memory and mood.” Soon the line will include body balms and gummies that function as both a sleep aid and an aphrodisiac, said Eric Blazak, the company’s founder and chief executive.What should older people know about cannabis?Because cannabis is not federally legal, doctors don’t have enough research to guide them on what conditions it is helpful for, who might be at higher risk for potential harms, how to dose it properly or which strains to recommend, said Dr. Benjamin Han, an addiction medicine specialist at the University of California, San Diego, and one of the few geriatricians in the United States who studies older adults and substance use.“What makes it even more complicated is cannabis is a very complex plant,” he added, and there are more than 100 cannabinoids — the biologically active components in the cannabis plant — as well as products with different ratios of THC to cannabidiol, or CBD.Start low and slow. If a patient wants to try cannabis products containing THC, Dr. Han recommends starting at a low dose (generally 1 milligram to 2.5 milligrams) and then “give it one week” before making the decision to increase it.Taking too many edibles can cause dizziness, confusion, changes in heart rate and blood pressure, panic attacks, anxiety, nausea, vomiting, and can even land some people in the emergency room.There’s also the potential for cannabinoid hyperemesis syndrome, a condition that causes recurrent vomiting in heavy marijuana users.One study, led by Dr. Han, found that emergency department visits associated with cannabis use among older adults rose more than 1,800 percent in California — from 366 in 2005 to 12,167 in 2019.Older users may lean on their prior experience with the drug, but “the cannabis today is very different,” he said. “It is stronger. And then on top of that, there are all these physiological changes with aging that make you more sensitive than you would have been 40 years ago.”Mr. Hickerson is experimenting with gummies to help him sleep longer. He often wakes up too early, around 4 a.m. Jackie Russo for The New York TimesDiscuss the risks and benefits with your doctor. “It’s important to talk with a clinician or health provider, especially if you’re using it for medical reasons to treat chronic disease or chronic symptoms,” Dr. Han said.Cannabis can interact with certain medications, like warfarin, a drug used to treat blood clots. And seniors who take sedative-hypnotics like Ambien or benzodiazepines like Xanax — or who drink alcohol — should consider avoiding cannabis, Dr. Solomon said, because when paired with those drugs, it can cause dizziness and confusion and make seniors more susceptible to falls and injuries.And smoking cannabis can trigger respiratory symptoms in those with chronic lung disease, Dr. Han added.Educate yourself. Ms. Verner recommended going to licensed dispensaries that sell products that have been tested by a third party. Familiarize yourself with state regulations, too, she said.“You just need to educate yourself, not be afraid of things — learn for yourself,” Ms. Verner said. “You need to know what may work for you — and you go from there.”Through trial and error, she discovered that cannabinol, or CBN, which is not psychoactive, was most helpful for her insomnia.Now she takes fewer pills: just one for her thyroid levels and another to reduce her blood pressure.Many older adults “end up with all these bottles of medicine,” she said. “And I don’t think that’s necessary.”

It’s the beef in your stew and the fish in your tacos; the eggs in your omelet and the beans on your nachos. Protein-rich foods play a starring role in any satisfying meal. And for good reason: Protein is essential for every function in your body.But how much protein do you really need? What are the best food sources? And how can you be sure you’re getting enough?Take this quiz to see how much you know.

Published9 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, SPLBy Fergus WalshMedical editorIn a world first, medical regulators in the UK have approved a gene therapy that aims to cure two blood disorders. The treatment for sickle cell disease and beta thalassemia is the first to be licensed using the gene-editing tool known as Crispr, for which its discoverers were awarded the Nobel prize in 2020. This is a revolutionary advance for two inherited blood conditions, both triggered by errors in the gene for haemoglobin. People with sickle cell disease produce unusually shaped red blood cells that can cause problems because they do not live as long as healthy blood cells and can block blood vessels, causing pain and life-threatening infections. People with beta thalassaemia do not produce enough haemoglobin, which is used by red blood cells to carry oxygen around the body. Patients with beta thalassemia often need a blood transfusion every few weeks of their lives.How it worksDNA is the blueprint of life – and genes contain the instructions for how every cell in our body works. Gene-editing allows the precise manipulation of DNA. The treatment involves removing bone marrow stem cells from a patient’s blood.In a laboratory, the gene-editing tool Crispr uses molecular scissors to make precise cuts in the DNA of the cells, thus disabling the faulty gene. The modified cells are infused back, allowing the body to start producing functioning haemoglobin.In trials, 28 out of 29 sickle cell patients were free of severe pain and 39 of 42 beta thalassemia patients no longer needed blood transfusions for at least a year. It’s hoped it could be a permanent fix.Trials are continuing in the UK, US, France, Germany and Italy.Around 15,000 people in the UK have sickle cell disease, most with an African or Caribbean family background. Almost 300 babies are born in the UK with sickle cell disease each year.More than 1,000 people in the UK are affected by thalassemia, mainly those of Mediterranean, southeast Asian and Middle Eastern origin.’The revolutionary gene-editing treatment that gave me new life'”Both sickle cell disease and beta thalassemia are painful, life-long conditions that in some cases can be fatal,” said Julian Beach, interim executive director of healthcare quality and access at the Medicines and Healthcare products Regulatory Agency (MHRA).”To date, a bone marrow transplant – which must come from a closely matched donor and carries a risk of rejection – has been the only permanent treatment option.”But now a “first-of-its-kind” gene-editing treatment called Casgevy has been authorised by the MHRA, he said.In trials, it has been “found to restore healthy haemoglobin production in the majority of participants with sickle-cell disease and transfusion-dependent beta thalassaemia, relieving the symptoms of disease”, he said.’I feel reborn after pioneering treatment’ Image source, Jimi OlaghereJimi Olaghere thought he would have to wait decades to be freed from his sickle cell disease – but he spoke to BBC News in 2022 after becoming one of the first seven sickle cell patients to have benefited from the revolutionary new gene-editing treatment in the US.”It’s like being born again,” said Jimi. He spoke of how he felt it had changed his life. “When I look back, it’s like, ‘Wow, I can’t believe I lived with that.'”Jimi had lived with sickle cell since childhood. “You always have to be in a war mindset, knowing that your days are going to be filled with challenges.”Read more here.John James OBE, Chief Executive of the Sickle Cell Society said: “Sickle cell disorder is an incredibly debilitating condition, causing significant pain for the people who live it and potentially leading to early mortality. “There are limited medicines currently available to patients, so I welcome today’s news that a new treatment has been judged safe and effective, which has the potential to significantly improve the quality of life for so many.” No price has yet been set for Casgevy, but the one off treatment might cost £1 million or more – which could be deemed too high a price for the NHS to bear. In April, a US think tank, ICER, said the drug would be cost effective if it was priced at no more than £1.5million.For Casgevy, the drug is a personalised one-off treatment made from tweaking the patient’s own cells – that makes it expensive and time-consuming. Add in the cost of research and development – there are just two labs one in the US and the other in the UK – currently producing the drug. The Boston-based pharma company involved, Vertex, will want its product used as widely as possible so will need to set a price that health services here and abroad are prepared to pay. THE DARK SIDE OF ONE OF THE MOST BEAUTIFUL PLACES ON EARTH: Shetland returns for a new series on BBC iPlayerWERE DINOSAURS TOO BIG?: Brian Cox and Robin Ince discover why size really matters if you want to avoid extinctionMore on this story‘I feel reborn after pioneering gene-editing treatment’Published20 February 2022

Published10 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, ReutersBy Vitaly ShevchenkoBBC MonitoringThe Kremlin has launched a wide-ranging campaign to force Ukrainians in occupied territories to become Russian, an investigation has found.Ukrainians are being denied healthcare and free movement unless they take up Russian citizenship, evidence suggests.The European Broadcasting Union (EBU), an alliance of public service media including the BBC, interviewed refugees for the investigation. They spoke of relentless pro-Russian propaganda in the occupied lands.One refugee from the occupied territories, Larysa, told the EBU’s Investigative Journalism Network that one of her friends was not provided with insulin for her diabetes – a key part of treatment – until she applied for a Russian passport. Another friend had to become a Russian citizen to have her broken arm treated, Larysa said. EBU Investigative Journalism NetworkPensions are not provided without Russian passports, food is not provided without Russian passports, and medical services are out of the questionLarysaUkrainian refugeeShe also spoke of other types of pressure forcing Ukrainians to assimilate as Russians. “Pensions are not provided without Russian passports, food is not provided without Russian passports, and medical services are out of the question. There are lots of checkpoints on the roads. And every time they stop you, they check your documents, and then say they will not let you through without a Russian passport next time.”So people have to obtain these papers. Because if someone, say, has cows in one village and sells milk in another, it is impossible to move between villages.”Larysa’s account of pressure to obtain Russian passports is corroborated by other refugees, such as Lyudmyla (not her real name) from the occupied part of Zaporizhzhia region.”When you go to a hospital you need to have a Russian passport. If you do not have a Russian passport, they won’t treat you. If you drive your own car and the patrol stops you, and you do not have a Russian passport, they can simply take your car away. So people are forced to obtain them. Retired people are forced to obtain Russian passports to receive pensions. It is a matter of survival.”Image source, Getty ImagesIn the past, Russia handed passports to residents of the breakaway Georgian regions of Abkhazia and South Ossetia, and later used them as part of its justification for invading Georgia in 2008.Russian curriculumBut Lyudmyla and her friend Oksana (also not her real name) say the main reason why they left their homes was because their children were being forced to study the Russian school curriculum.”We were provoked into leaving by the opening of a Russian school, and we were being forced to go there. They told us that if we did not let our children go there, they would take our children away and deprive us of our parental rights. “When you send your children to the school, you must have a Russian passport. If you do not have a Russian passport your child will have problems and you will have problems. “What kind of problems? You will be stripped of your parental rights. They will take our children away and that’s it – you will be left without children,” Lyudmyla says.Image source, EBU Investigative Journalism NetworkEarlier in 2023, Russia unveiled new schoolbooks which aim to justify its invasion of Ukraine. They falsely portray Ukraine as an aggressive state run by nationalist extremists and manipulated by the West, which allegedly uses the country as a “battering ram” against Russia.Oksana says she left also because she was afraid that her 20-year-old son would be drafted into the Russian army and forced to fight Ukrainians.PropagandaHistorian Artem Petryk was in the southern city of Kherson when it was occupied by Russians between February and November 2022. He described the Russian authorities’ concerted efforts to influence the hearts and minds of the local population.EBU Investigative Journalism NetworkThey introduced the Russian school curriculum, crucially the history course, and tried to impose Russia’s world viewArtem PetrykHistorian”From the first days of the occupation, they seized control of television and began broadcasting Russian radio. There was a stream of fakery about Ukraine and the West. It glorified the Russian army and the Russian state.”And everywhere in the city they put up billboards with portraits of Russian tsars, commanders, and there were slogans saying that Kherson is a city with a Russian history, Russia is here forever, and so on. “They tried to impose the Russian identity through the public space. They marked days of the Russian flag, days of Russia, put up billboards and, of course, tried to establish control over school. They introduced the Russian school curriculum, crucially the history course, and tried to impose Russia’s world view,” Mr Petryk says.Larysa describes Russification efforts by the occupying authorities as another weapon used by Russia.”This is the same as weapons – not the ones which shoot, but moral ones. Sometimes these moral weapons hurt harder than a machine gun. Because machine guns fire once and it’s done, but the moral ones oppress you every day. This is very hard,” Larysa says. More on this storyUkrainian teen who received call-up to Russian armyPublished5 days agoRussia goes back to prisons to feed its war machinePublished26 OctoberThe last residents of a bitterly contested Ukrainian townPublished24 October

Our DNA is not indestructible. Throughout the course of our lives, DNA can break in response to natural and environmental factors. Thankfully, our bodies have dedicated enzymes and pathways which can glue our broken DNA back together through several different mechanisms, known as DNA repair pathways.
Some cancers, however, can hijack these pathways for their own benefit. Susanna Stroik, PhD, and Dale Ramsden, PhD, both researchers in the Department of Biochemistry and Biophysics in the UNC School of Medicine and the UNC Lineberger Comprehensive Cancer Center, have pieced together the lesser-known DNA repair pathway, called polymerase theta-mediated end joining (TMEJ).
The pathway — which has been found to be upregulated in many patients with hereditary breast cancer, ovarian cancer, and prostate cancer, specifically those involving BRCA1 and BRCA2 mutations — has been laid out step by step in a published article in Nature, and the new knowledge could lead to new therapies for cancer.
“People with these breast cancer mutations, their cancers rely on polymerase theta’s repair pathway to keep the tumors alive and repair DNA damage in the cancerous tissue,” said Stroik, a postdoctoral researcher in Ramsden’s lab. “Now that we know more about this pathway, scientists could, in theory, produce a drug that could disrupt key pieces of the pathway in cancer cells, as opposed to using conventional chemotherapies that destroy healthy cells along with the cancer.”
Polymerase Theta’s Discovery
Out of all DNA repair pathways, TMEJ has been the most elusive. Richard Wood, PhD, a distinguished professor at University of Texas MD Anderson Cancer Center played a key role in the first characterization of polymerase theta in 2003.
Over the next 15 years, multiple labs, including the Wood, Ramsden, and Gupta labs (also at Lineberger Comprehensive Cancer Center), were able to link polymerase theta to DNA repair (TMEJ) and cancer. Sylvie Doublié, PhD, an alumnus of UNC-Chapel Hill and professor of microbiology and molecular genetics at the University of Vermont, then solved the first structure of polymerase theta.

Together, and with other scientists from Penn State and New York University, these researchers were dedicated to understanding precisely what steps are involved in TMEJ, and which of those steps polymerase theta does and does not perform.
With the help of these collaborators, Stroik was able to use a wide variety of cutting-edge experimental approaches to fill in the gaps in our understanding of the TMEJ pathway. Critically, she discovered that another polymerase, called polymerase delta, uses a buddy system with polymerase theta to assist it in this repair pathway.
A Unique Buddy System
Stroik’s research showed that polymerase theta is good at some things, but not others.
“It makes a lot of errors and it’s not capable of creating large swaths of DNA at once,” said Stroik. “What was so beautiful and kind of elegant about the whole discovery is that there are two different enzymes alternating between pathway steps and helping each other out.”
When a double stranded break occurs, both strands of DNA are cut at the same spot, much like scissors severing a braid of hair. Polymerase theta acts quickly, grabbing the two single strands of DNA, matching up the closest base pairs to the break, and holding them together.

However, this often leaves some residual flaps of single stranded DNA at the ends. Polymerase delta jumps in to cut the extraneous flaps, giving polymerase theta enough room to start synthesizing new DNA to fill in gaps in the DNA strands. Finally, polymerase delta jumps in one last time to help polymerase theta complete synthesis.
Stroik had another breakthrough finding: polymerases theta and delta are physically attached to one another. This new information could prove to be especially useful to drug developers hoping to create a new cancer treatment by drugging this interaction.
Cancer Treatment Potential
Since many cancers make use of the TMEJ pathway to keep tumors alive, many researchers have investigated creating drugs that can interfere with the pathway, essentially preventing cancer from repairing itself, leading to its eventual demise.
“Anytime you find new pieces of the pathway, you can ‘drug’ it,” said Ramsden.
Stroik and Ramsden’s new research will contribute to ongoing basic studies in polymerases theta and delta, while also aiding new cancer drugs called polymerase theta inhibitors, which are currently in clinical trials.

T cells are the key immune system component involved in killing cancer. Tumors produce signals that turn off these T cells, partially by forcing them to progressively differentiate (mature) into a hypofunctional state known as exhaustion. Scientists from St. Jude Children’s Research Hospital comprehensively examined the transcription factors involved in T-cell differentiation states in cancer. They then used this information to enhance anticancer activity in preclinical models by promoting or blocking T-cell differentiation. The findings, which have implications for cancer immunotherapy, were published today in Nature.
T cells are used in adoptive cell therapy (ACT) to target and kill cancer cells. Among ACTs, chimeric antigen receptor (CAR) T cells have shown clinical efficacy in blood cancers but have not been as effective in solid tumors. This variance in efficacy is partly because tumors promote T-cell exhaustion, in which the cells are less effective at actively killing cancer. The scientists showed they could precisely interrupt the flow of the differentiation process, thereby enhancing antitumor efficacy.
“T cells are the cornerstone of tumor immunotherapy, and we found a new way to reprogram T cells to make them more effective,” said Hongbo Chi, Ph.D., St. Jude Department of Immunology. “We can push them towards a specialized state so that they can be more functional tumor-killing cells.”
Modifying differentiation to flow toward cancer-killing T cells
T-cell differentiation is conceptually similar to a river running down a mountain. The top of the mountain is the precursor cell, and the bottom an exhausted cell. The desired state is between these two extremes — like having a lake in the middle of the mountain — that is differentiated enough, but not too much, to have high proliferation and effective anticancer activity. The lake receives water from above but also has a stream constantly draining it further down the slope. Uninterrupted, all water in the lake will eventually drain through the river leading down below — all the T cells will become exhausted.
The scientists found a way to increase the water flow from above and dam the river draining the lake, resulting in more water accumulation in the lake or, more aptly, more T cells that effectively kill tumors. For example, when the researchers deleted the transcription factor ETS proto-oncogene 1 (ETS1), the amount of cancer-killing T cells was increased by enhancing differentiation to the intermediate state (increasing flow into the lake). On the other hand, knocking out the transcription factor recombination signal binding protein for immunoglobulin kappa J region (RBPJ) increased the accumulation of intermediate state T cells by blocking terminal differentiation (damming the river at the lake). Each approach showed markedly increased antitumor activity.
Even more promising, when the researchers combined their modified T cells with a type of immunotherapy called immune checkpoint blockade, they further increased antitumor activity.

“We’ve provided new potential strategies to enhance immunotherapy,” said co-first author Peipei Zhou, Ph.D., St. Jude Department of Immunology. “We increased the amount of cancer-killing T cells by differentiating them from upstream precursors, and we could also block terminal differentiation to increase accumulation of the functional cells. Both approaches improved antitumor efficacy in our immune checkpoint blockade models.”
While the work was done in mouse models, the researchers used bioinformatics data from human clinical samples to verify that these same genes are important in these processes in humans.
Mapping the differentiation journey of exhausted T cells
T cells infiltrate tumors to go about their work of destroying them. The researchers mapped the transcription factors expressed in the T cells infiltrating tumors. Their work showed which individual transcription factors and their networks are responsible for each T cell differentiation state, providing targets for improving immunotherapy.
“We created a map for the field of T-cell differentiation and exhaustion in tumors based on the loss-of-function genetic screening at high dimension,” said co-first author Hao Shi, Ph.D., St. Jude Department of Immunology. “This map will provide a guide for future researchers to refer to and use to identify ways to improve T cell-based immunotherapies.”
Where past attempts to understand T-cell exhaustion focused on an individual molecule or transcription factor, this screen was more comprehensive. This allowed the researchers to document the entirety of the gene regulatory networks involved.

“We’ve provided the most complete picture of the transcription factors in T cells inside a tumor ever created,” Zhou said.
“Such a causal transcriptional network provides new insights into lineage differentiation, a fundamental process in biology,” added Shi.
The group performed this feat using single-cell CRISPR-Cas9 screening, a gene editing technology that analyzes gene expression profiling of individual cells after selectively removing transcription factors in a comprehensive screen. Transcription factors are proteins that directly regulate gene expression. By examining an individual T cell’s gene expression pattern, the researchers could compare them to see which knocked-out transcription factors most affected T-cell differentiation and anticancer activity.
“The same approach may be more broadly applicable to increase our knowledge in many biological contexts beyond T cells and immunology,” Chi said. “We showed this new technology, single-cell CRISPR screening in vivo, can drive novel biological discovery. I think we’re at the advent of something truly exciting.”

Weight influences how and when bodies burn energy, new research indicates.
An Oregon Health & Science University study published in the journal Obesity found people who have a healthy weight use more energy during the day, when most people are active and eat, while those who have obesity spend more energy during the night, when most people sleep. The study also found that during the day, those with obesity have higher levels of the hormone insulin — a sign that the body is working harder to use glucose, an energy-packed sugar.
“It was surprising to learn how dramatically the timing of when our bodies burn energy differed in those with obesity,” said the study’s first author, Andrew McHill, Ph.D., an assistant professor in the OHSU School of Nursing and the Oregon Institute of Occupational Health Sciences at OHSU. “However, we’re not sure why. Burning less energy during the day could contribute to being obese, or it could be the result of obesity.”
Obesity is defined as having a Body Mass Index, or BMI, of 30 or more. Being overweight or obese increases the risk for health conditions such as high blood pressure and Type 2 diabetes.
Schedules and when people sleep, eat and exercise can also affect health, by either complementing or going against the body’s natural, daily rhythms. Every 24 hours, people experience numerous changes that are triggered by the human body’s internal clock. These changes normally occur at certain times of the day in order to best serve the body’s needs at any given hour.
McHill and the study’s senior author, Steven A. Shea, Ph.D., director of the Oregon Institute of Occupational Health Sciences at OHSU, focus their research on how circadian rhythms and sleep impact the human body. McHill leads theOHSU Sleep, Chronobiology and Health Laboratory.
While previous research has suggested circadian rhythm misalignment affects energy metabolism and glucose regulation, those studies have largely involved participants who have a healthy weight. To explore this further, McHill, Shea and colleagues organized a study that included people of different body sizes.
A total of 30 people volunteered to participate in the study, which involved participants staying at a specially designed circadian research lab for six days. The study followed a rigorous circadian research protocol involving a schedule designed to have participants be awake and sleep at different times throughout each day.
After each period of sleep, volunteers were awakened to eat and participate in a variety of tests for the remaining time of each day. One test had participants exercise while wearing a mask that was connected to a machine called an indirect calorimeter, which measures exhaled carbon dioxide and helps estimate energy usage. Blood samples were also collected to measure glucose levels in response to an identical meal provided during each day.
Next, the research team plans to explore eating habits and hunger in people who are obese, as well as those who have a healthy weight. That new study will also follow up on a 2013 study, led by Shea, that found circadian clocks naturally increase food cravings at night.