Publisher Health

Researchers have demonstrated that a transplant surgical procedure (called ‘needle trauma’) triggers a profound immune response and causes the death of most grafted dopamine neurons. They also found that co-transplantation of neuronal cell therapy with host regulatory T cells resulted in effective suppression of needle trauma and significant improvement in the survival and recovery of grafts. These findings suggest a path for the ‘realistic’ use of cell therapy to treat neurodegenerative disorders.
Cell therapy holds promise as a new treatment for Parkinson’s disease but, in many trials to date, most transplanted dopamine cells have failed to survive, raising a fundamental obstacle. Recent advancements led by researchers at Mass General Brigham could change this. Investigators used regulatory T cells to supplement neuronal cell therapy and decrease adverse effects of the surgical procedure in rodent models. Results from the team, which includes investigators from McLean Hospital and Massachusetts General Hospital, are published in Nature.
“We have been investigating personalized, stem-cell based therapies that reprogram a patient’s own cells to treat their Parkinson’s,” said corresponding author Kwang-Soo Kim, PhD, of the Molecular Neurobiology Laboratory at McLean Hospital. “We have now made a major breakthrough using immune cells to improve delivery, survival, and recovery for neuronal cell therapies. Our findings show the power and flexibility of cell therapy to be modified and enhanced to become a realistic modality to treat conditions like Parkinson’s.”
In the United States, only Alzheimer’s disease is a more common neurodegenerative disorder than Parkinson’s disease, which is characterized by loss of midbrain dopaminergic neurons. The current standard of care is dopamine replacement therapy, which addresses only symptoms like tremors or stiffness with substantial side effects.
Since the 1980s, cell therapies have faced a significant barrier: poor graft survival. Researchers have proposed diverse mechanisms to explain the cell death and added various modifications to improve cell survival. Three years ago, Kim’s team demonstrated that personalized cell therapy could be used to replace dopamine neurons in the first personalized cell therapy in a sporadic Parkinson’s disease patient. However, their results were restricted to a single patient and limited graft survival remained a key challenge.
In their current study, Kim and colleagues hypothesized that regulatory T cells — which maintain immune homeostasis, contain inflammation, and prevent immune rejection — could be co-transplanted with the neurons to mitigate needle trauma and improve cell survival and disease recovery. To test this, the researchers first transplanted midbrain dopaminergic neurons in previously validated mouse and rat models of Parkinson’s disease. They observed how the surgical procedure resulted in acute inflammation and an adverse immune response in the brain tissue, which they termed “needle-trauma.”
Next, they co-transplanted regulatory T cells with the dopaminergic neurons. They measured the survival of grafted neurons over two weeks. After five months, they reassessed this finding and observed how the grafted area was recovering.

“Initially, just one or two weeks after transplantation, the majority of the dopamine neurons died, rendering the cell therapy unsuccessful,” said Kim. “But when we added regulatory T cells to the transplant, survival of the grafted dopamine neurons increased. Also, behavior recovery was faster and more robust.”
Regulatory T cells not only improved the survival of grafted dopaminergic neurons but also significantly suppressed the outgrowth of non-dopaminergic cells, including reactive inflammatory cells, in host brains.
“This finding is very significant because a potential hazard associated with cell transplantation is often the outgrowth of undesirable, potentially harmful cells,” Kim said. “The most important criterion for cell therapy is safety.”
The needle trauma induced significant brain cell death. However, the regulatory T cells were able to suppress the death, along with the adverse neuroinflammation and unwanted peripheral immune cells entering the injury site.
“Needle trauma is a universal issue in cell therapies in the nervous system, not just for dopaminergic neurons or Parkinson’s disease,” said Bob Carter, MD, PhD, the chief of Neurosurgery at the Mass General Hospital and a co-author of the current paper. “Our principles can be applied widely to any cell therapy for other (neuro)degenerative disorders such as Alzheimer’s, ALS, or Huntington’s.”
Limitations of the study include being constrained to rodent models. Kim says the next steps are to understand the safety of these transplants, exactly how regulatory T cells improve the survival of dopaminergic neurons, and how to optimize their function.
Recently, Mass General Brigham launched its Gene and Cell Therapy Institute to help translate scientific discoveries made by researchers like Kim into first-in-human clinical trials and, ultimately, life-changing treatments for patients.

Like its viral cousins, a somewhat parasitic DNA sequence called a retrotransposon has been found borrowing the cell’s own machinery to achieve its goals.
In a new work appearing online Wednesday in the journal Nature, a Duke University team has determined that retrotransposons hijack a little-known piece of the cell’s DNA repair function to close themselves into a ring-like shape and then create a matching double strand.
The finding upends 40 years of conventional wisdom saying these rings were just a useless by-product of bad gene copying. It may also offer new insights into cancer, viral infections and immune responses.
Retrotransposons are segments of DNA around 7,000 letters long that copy and paste themselves into different parts of the genomes of both plants and animals. By doing this, they play a role in rewriting DNA and regulating how the cell uses its genes. Retrotransposons are believed to be behind a lot of the variation and innovation in genes that drives evolution, and are inherited from both parents.
Many studies have suggested that these rings of DNA outside the chromosomes are somehow involved in the development and progression of cancer in part because they are known to harbor cancer-driving oncogenes within their DNA sequences. The retrovirus HIV, which causes AIDS, is also known to form circular DNA.
“I think these elements are the source of genome dynamics, for animal evolution and even to affect our daily lives,” said Zhao Zhang (ZZ), an assistant professor of pharmacology and cancer biology and a Duke Science & Technology scholar. “But we are still in the process of appreciating their function.”
Retrotransposons are quite common — they make up about 40% of the human genome, and more than 75% of the maize genome — but how and where they copy themselves has always been a bit murky.

Zhang holds up a thick textbook on retroviruses that he consulted for this study. The books say the ring-like sequences are “created by recombining the two ends of linear DNA, and are just a dead end, a by-product of failed replication,” he said.
In earlier work with fruit fly eggs, Zhang’s team had established that inherited retrotransposons use the ‘nurse cells’ which support the egg as factories to manufacture many copies of themselves that are then distributed throughout the genome in the fly’s developing egg. This model system allowed the researchers to zoom in still further to learn more about retrotransposons.
In the latest work, they found unexpectedly that most newly added retrotransposons were in this circular form rather than being integrated into the host’s genome. Then they ran a series of experiments knocking out the cell’s DNA repair mechanisms one at a time to figure out how and where the circles are being formed.
The answer: A little-studied DNA repair mechanism called alternative end-joining DNA repair, or alt-EJ for short, which repairs doubles-stranded breaks. The retrotransposon sequences were using this part of the host’s repair machinery to sew the ends of their single-stranded DNA together and then using its DNA synthase to create a matching double-strand. For good measure, the researchers confirmed that this is also the process within human cells.
So retrotransposons aren’t a sloppy accident; they’re actually hijacking a little bit of the cell’s machinery to manufacture more of themselves, just like viruses do.

“Our discovery actually overturns the textbook model,” Zhang said. “We showed that the recombination event proposed by the textbook is not important to forming rings,” Zhang said. “Instead, it’s the alt-EJ pathway driving circle production.”
“My lab currently is trying to test whether circular DNA can be an intermediate to make new genome insertions,” Zhang said. “We’re also testing whether circular DNA can be sensed by our immune system to trigger an immune response.”
“In the retroviral field and retrotransposon field, people think circular DNA is just a minor event, but our study is bringing circular DNA into the center stage,” Zhang said. “People should pay more attention to circular DNA.”
Funding for this study came from the National Cancer Institute (P01CA247773), National Institutes of Health (DP5 OD021355, R01 GM141018) and the Pew Biomedical Scholars Program.

The function of mast cells, which are part of the immune system, is still a mystery. Scientists at the German Cancer Research Center (DKFZ) have now shown in mice: mast cells function as a sensor that signals the animals to avoid antigens, including harmful allergens, and thereby protect themselves from health-threatening inflammatory reactions. The findings were published in the journal Nature.
Mast cells are found primarily in tissues that separate the outside and inside worlds of the body, such as the epithelia of the gastrointestinal tract and lungs. Within the tissues, mast cells often reside near nerve endings. Mast cells are well known to persons suffering from allergies because they secrete messenger substances such as histamine, which cause annoying to health-threatening allergic symptoms. These symptoms occur when mast cells are activated by IgE class antibodies during repeated antigen contact.
“Why mast cells and IgE exist at all has not yet been conclusively explained,” says Hans-Reimer Rodewald. The DKFZ immunologist and his team have now been able to show for the first time in mice, in a combination of behavioral experiments and immunological studies, that mast cells act like a sensor that helps to avoid contact with allergens
No antigen avoidance without mast cells and IgE
The DKFZ researchers immunized mice with the allergen ovalbumin, a protein component of chicken egg white. They then gave the animals the free choice of preferring either normal or egg white-containing drinking water. Immunized animals avoided the egg white-enriched water, while their non-immunized conspecifics clearly preferred it. A large proportion of the immunized animals avoided the egg white-containing water already one day after immunization, some mice even after the first sip.
However, when the scientists performed this behavioral test with mice that genetically lack mast cells, both immunized and non-immunized animals preferred the egg white-containing water. Mice genetically unable to produce IgE also showed no avoidance behavior. Thus, both components — mast cells and IgE — are responsible for antigen avoidance.
When the immunized mice had no choice because the egg white solution was instilled in them, the animals developed inflammation in the stomach and small intestine. “The avoidance behavior mediated by mast cells apparently protects the animals from harmful immune reactions,” explains Thomas Plum, one of the first authors.
How do mast cells “talk” to the brain?
An important open question for the scientists was now: How can mast cells, as a component of the immune system, influence behavior? In what ways do immune cells “talk” to the brain? The scientists examined a variety of biologically active substances released by mast cells. These include leukotrienes, pro-inflammatory messengers known to activate sensory nerves. If the researchers blocked leukotriene synthesis, the immunized mice no longer showed the same consequence in avoiding egg white. Leukotrienes therefore appear to be at least partly involved in avoidance behavior. Further immunological and neurobiological experiments are needed in the future to identify the nerve connections through which the mast cell signal is reported to the brain.
“In the intestine, lungs or skin, immune reactions against non-infectious antigens can occur as a result of so-called barrier disorders, permeability of the tissues from the outside to the inside. In the case of allergy, we call such antigens allergens. Whether these substances are dangerous or not, it is important for the organism to avoid their further intake in order to prevent inflammatory diseases. This is an evolutionary advantage and finally a conclusive explanation of the physiological role of mast cells and IgE,” Rodewald summarizes the results.
Whether mast cells also contribute to the avoidance of harmful antigens in humans must be addressed in further studies.

In a new study, published today (12 July) in Nature, researchers have produced the most detailed and comprehensive human Heart Cell Atlas to date, including the specialised tissue of the cardiac conduction system — where the heartbeat originates.
The multi-centre team is led by the Wellcome Sanger Institute and the National Heart and Lung Institute at Imperial College London, and has also presented a new drug-repurposing computational tool called Drug2cell, which can provide insights into the effects of drugs on heart rate.
This study is part of the international Human Cell Atlas* (HCA) initiative, which is mapping every cell type in the human body, to transform our understanding of health and disease, and will form the foundation for a fully integrated HCA Human Heart Cell Atlas.
Charting eight regions of the human heart, the work describes 75 different cell states including the cells of the cardiac conduction system — the group of cells responsible for the heartbeat — not understood at such a detailed level (1) in humans before. The human cardiac conduction system, the heart’s ‘wiring’, sends electrical impulses from the top to the bottom of the heart and coordinates the heartbeat.
By using spatial transcriptomics, which gives a “map” of where cells sit within a tissue, researchers were also able to understand how these cells communicate with each other for the first time. This map acts as a molecular guidebook, showing what healthy cells look like, and providing a crucial reference to understand what goes wrong in disease. The findings will help understand diseases such as those affecting the heart rhythm.
The assembly of a Human Heart Cell Atlas is key given that cardiovascular diseases are the leading cause of death globally. Around 20,000 electronic pacemakers are implanted each year in the UK for these disorders (2). These can be ineffective and are prone to complications and side-effects (3). Understanding the biology of the cells of the conduction system and how they differ from muscle cells paves the way to therapies to boost cardiac health and develop targeted treatments for arrhythmias.

The team also presents a new computational tool called Drug2cell. The tool can predict drug targets as well as drug side effects. It leverages single-cell profiles and the 19 million drug-target interactions in the EMBL-EBI ChEMBL database.
Unexpectedly, this tool identified that pacemaker cells express the target of certain medications, such as GLP1 drugs, which are used for diabetes and weight loss and are known to increase the heart rate as a side-effect, the mechanism of which was unclear. This study suggests that the increase in heart rate might be partly due to a direct action of these drugs on pacemaker cells, a finding the team also showed in an experimental stem cell model of pacemaker cells.
Dr James Cranley, joint first author, a cardiologist specialising in heart rhythm disorders and PhD student at the Wellcome Sanger Institute, said: “The cardiac conduction system is critical for the regular and coordinated beating of our hearts, yet the cells which make it up are poorly understood. This study sheds new light by defining the profiles of these cells, as well as the multicellular niches they inhabit. This deeper understanding opens the door to better, targeted anti-arrhythmic therapies in the future.”
Dr Kazumasa Kanemaru, joint first author and Postdoctoral Fellow in the Gene Expression Genomics team at the Wellcome Sanger Institute, said: “The mechanism of activating and suppressing pacemaker cell genes is not clear, especially in humans. This is important for improving cell therapy to facilitate the production of pacemaker cells or to prevent the excessive spontaneous firing of cells. By understanding these cells at an individual genetic level, we can potentially develop new ways to improve heart treatments.”
The study unearthed an unexpected discovery: a close relationship between conduction system cells and glial cells. Glial cells are part of the nervous system and are traditionally found in the brain. They have been explored very little in the heart. This research suggests that glial cells are in physical contact with conduction system cells and may play an important supporting role: communicating with the pacemaker cells, guiding nerve endings to them, and supporting their release of glutamate, a neurotransmitter.

Another key finding of the study is an immune structure on the heart’s outer surface. This contains plasma cells, which release antibodies into the space around the heart to prevent infection from the nearby lungs. The researchers also identified a cellular niche enriching for a hormone (4) that could be interpreted as an early warning sign of heart failure.
Dr Michela Noseda, senior Lecturer in Cardiac Molecular Pathology at the National Heart and Lung Institute, Imperial College London, a Coordinator of the Human Cell Atlas Heart BioNetwork and a lead author, said: “We often don’t fully know what impact a new treatment will have on the heart and its electrical impulses — this can mean a drug is withdrawn or fails to make it to the market. Our team developed the Drug2cell platform to improve how we evaluate new treatments and how they can affect our hearts, and potentially other tissues too. This could provide us with an invaluable tool to identify new drugs which target specific cells, as well as help to predict any potential side-effects early on in drug development.”
Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation, which part-funded the research with the German Centre for Cardiovascular Research (DZHK), said: “Using cutting-edge technologies, this research provides further intricate detail about the cells that make up specialised regions of the human heart and how those cells communicate with each other. The new findings on the heart’s electrical conduction system and its regulation are likely to open up new approaches to preventing and treating rhythm disturbances that can impair the heart’s function and may even become life-threatening.”
“International collaboration is key to scientific progress. This impactful study and other discoveries from the broader Human Cell Atlas initiative are excellent examples of what can be achieved when the international research community works together across borders. Our combined efforts can ultimately produce better outcomes for patients worldwide.”
Dr Sarah Teichmann, a senior author of the study from the Wellcome Sanger Institute and co-chair of the Human Cell Atlas Organising Committee, said: “This Heart Cell Atlas reveals cardiac microanatomy in unprecedented detail, including the cardiac conduction system that enables each heartbeat, and is a valuable reference for studying heart disease and designing potential therapeutics. An important contribution to the global Human Cell Atlas initiative, which is mapping every cell type in the body to understand health and disease, it will form the foundation for a fully integrated HCA Human Heart Cell Atlas. In addition, our suite of computational methods will help identify possibilities for repurposing existing drugs to treat diseases in other tissues.”
More information can be found at https://www.humancellatlas.org/

Simply the smell of seafood can make those with an allergy to it violently ill — and therefore more likely to avoid it. The same avoidance behavior is exhibited by people who develop food poisoning after eating a certain meal.
Scientists have long known that the immune system played a key role in our reactions to allergens and pathogens in the environment, but it was unclear whether it played any role in prompting these types of behaviors towards allergic triggers.
According to Yale-led research published July 12 in the journal Nature, it turns out that the immune system plays a crucial role in changing our behaviors.
“We find immune recognition controls behavior, specifically defensive behaviors against toxins that are communicated first through antibodies and then to our brains,” said Ruslan Medzhitov, Sterling Professor of Immunobiology at Yale School of Medicine, investigator for the Howard Hughes Medical Institute, and senior author of the study.
Without immune system communication, the brain does not warn the body about potential dangers in the environment and does not try to avoid those threats, the study shows.
A team in the Medzhitov lab, led by Esther Florsheim, at the time a postdoctoral researcher at Yale and now an assistant professor at Arizona State University, and Nathaniel Bachtel, a graduate student at the School of Medicine, studied mice that had been sensitized to have allergic reactions to ova, a protein found in chicken eggs. As expected, these mice tended to avoid water laced with ova, while control mice tended to prefer ova-laced water sources. The aversion to ova-laced water sources in sensitized mice lasted for months, they found.
The team then examined whether they could alter the behavior of sensitized mice by manipulating immune system variables. They found, for instance, that mice allergic to ova lost their aversion to the protein in their water if Immunoglobulin E (IgE) antibodies, produced by the immune system, were blocked. IgE antibodies trigger the release of mast cells, a type of white blood cell that, along with other immune system proteins, plays a crucial role in communicating to areas of the brain that control aversion behavior. Without IgE as an initiator, the transmission of information was interrupted, so that mice no longer avoided the allergen.
Medzhitov said that the findings illustrate how the immune system evolved to help animals avoid dangerous ecological niches. Understanding how the immune system memorizes potential dangers, he added, could one day help suppress excessive reactions to many allergens and other pathogens.

The ship, by some measures the world’s largest, will depart from Miami in January on its maiden voyage. Some can’t wait to board. Others call it a “monstrosity” that is bad for the environment.When the Icon of the Seas sets sail early next year, it will take some time to disappear from the horizon. At 1,198 feet long and a gross tonnage of 250,800, it is hard to miss.The Royal Caribbean cruise ship will have 20 decks packed with more than 20 bars and restaurants, seven pools, nine whirlpools, and six water slides, as well as mini golf, rock climbing and an arcade. It will carry up to 7,960 people — up to 5,610 guests and a crew of 2,350 to pour drinks, turn back covers, swab the decks and keep the vessel on course.Since Royal Caribbean announced this newest ship last year, it has helped to boost the company’s sales with high demand for advanced bookings.It has also become an object of fascination (and scorn) on social media.Some can’t wait to climb aboard, with rooms already selling out for the ship’s first voyage. But others have criticized its size and bright colors, calling it a “monstrosity.” One critic called an artist’s rendering a “Candy Crush version of the dystopian underground world” from science-fiction series “Silo” on Apple TV+.Some critics even drew comparisons to an ill-fated ocean liner of yesteryear, noting it is five times “larger and heavier than the Titanic,” and about 300 feet longer.Royal Caribbean bills the older Wonder of the Seas as the “biggest ship in the world.” When the new one is ready, it will be 10 feet longer, heavier and will carry more people, perhaps giving it bragging rights as the world’s largest.Royal Caribbean said in a statement last month that the Icon of Seas had passed its first round of sea trials, traveling in the open ocean for the first time near Turku, Finland. The ship will have another round of trials later this year ahead of its debut in January, the company said.Interest in the ship comes as the cruise industry tries to bounce back from the coronavirus pandemic, when multiple outbreaks onboard ships led the Centers for Disease Control and Prevention to chastise the industry and ban cruises.But now the voyages have resumed and vacationers have returned to the sea, even as the industry still faces health and environmental concerns.This year, for example, the C.D.C. has recorded 13 norovirus outbreaks on cruise ships, four of them on Royal Caribbean International cruises.And environmentalists like Marcie Keever, program director of oceans and vessels at Friends of the Earth in Washington, contend that cruise lines “continue to build bigger ships that rely on fossil fuels, dump toxic wastewater into our oceans and burden coastal communities with air, water and garbage pollution.”Royal Caribbean referred a request for comment on Tuesday seeking more details about the ship to its website. The company said it could not comment about environmental concerns, citing a quiet period required ahead of its next earnings report.However, the company has touted the effect that the Icon of the Seas is already showing on its bottom line, saying in a statement that advance bookings during the first quarter were ”significantly higher” than the first quarter of 2019.Jason Liberty, president and chief executive of Royal Caribbean Group, said during an earnings call in May that the Icon of the Seas has been “significantly more booked” for its inaugural season “than any other Royal Caribbean ship launch.”Michael Bayley, president and chief executive of Royal Caribbean International, said during the call that the ship was “the best performing new product launch we’ve ever had in the history of our business.”“It’s really driving a huge amount of demand,” Mr. Bayley said.

Senator Chuck Schumer, the majority leader, has asked the F.D.A. to investigate a popular beverage created by the YouTube influencers Logan Paul and KSI over its high caffeine content.The release of Prime, a drink brand founded by the YouTube personality and boxer Logan Paul, had British teenagers lining up for hours outside grocery stores on its release date in December. Some supermarkets were even forced to limit purchases to one bottle per customer.Now, Prime is facing a backlash from physicians and lawmakers who say that the high levels of caffeine in one of its drinks can be harmful to children. At a news conference in New York on Sunday, Senator Chuck Schumer, the majority leader, called for the Food and Drug Administration to investigate the ultra-caffeinated variety of Prime, which he pointed out has caffeine levels equivalent to about six 12-ounce cans of Coca-Cola.Prime offers two kinds of beverages: Prime Hydration, a sports drink that does not contain caffeine, and Prime Energy, a highly caffeinated drink. A 12-ounce Prime Energy contains 200 milligrams of caffeine, compared with the 114 milligrams of caffeine in a 12-ounce can of Red Bull or the 100 milligrams found in a cup of coffee. Pediatricians recommend that children under the age of 12 avoid caffeine entirely, and those from 12 to 18 should consume no more than 100 milligrams per day.Senator Schumer said Prime Energy had “so much caffeine in it, that it puts Red Bull to shame.” He added that Prime differed from other highly caffeinated energy drinks in that its advertising campaign appeared to target those under 18.Mr. Paul, a high-profile provocateur known for his controversial videos, has long faced questions over the example he sets for young people. He has won two Teen Choice awards, decided mainly by voters ages 13 to 19, and when he is pursued by his loyal fans, known as the Logang, they often skew young. He launched Prime in 2022 with Olajide Olayinka Williams Olatunji, a 30-year-old rapper and another prominent YouTube personality known by his online alias, KSI.In a letter to Dr. Robert Califf, head of the F.D.A., on Monday, Senator Schumer urged the agency to investigate the beverage company.“Many physicians have serious concern for Prime, and I write to specifically urge your agency to investigate Prime for its claims, marketing and caffeine content,” Senator Schumer wrote.Prime said in a statement to The New York Times that each can of its energy drink “states clearly” that it was not made for anyone under the age of 18. The company added that the beverage had caffeine levels comparable to other top-selling energy drinks and that Prime was compliant with F.D.A. guidelines.The official backlash comes as America’s major beverage companies vie for a piece of the rapidly growing market for energy drinks. Over the past five years, sales in the energy drink industry have surged from $12 billion to $19 billion, according to Circana, a market research firm. Recently, companies like Pepsi and Gatorade have both invested in new caffeine-addled beverage lines, and shares of Monster Energy, another caffeinated beverage, surged 30 percent in the past year. Experts say the excitement has been fueled in part by a decades-long pivot away from sugary sodas.Senator Schumer said at the Sunday news conference that parents had brought Prime to his attention. But the energy drink is part of a growing field of high-caffeine drinks popular among young people on TikTok. These drinks include the brand Alani Nu, supported by the social media influencer Addison Rae, and Celsius, which is backed by Pepsi.Dr. Edith Bracho-Sanchez, a pediatrician at NewYork-Presbyterian Hospital who joined Senator Schumer at the news conference on Sunday, wrote in an email to The Times that regularly consuming as much caffeine as is found in Prime Energy can disrupt the sleep cycle, which is essential to a child’s developing brain.High caffeine consumption can also give consumers the jitters and cause digestive issues, headaches, heart palpitations and even abnormal heart rhythms, she added.Mr. Paul rose to fame as a popular YouTube personality and has since ventured into other avenues such as acting and boxing.Representatives for Mr. Paul did not immediately reply to a request for comment.A Prime representative said in a statement that it was “very important” to distinguish between the two drinks on the market, one of which — Prime Hydration — was also immensely popular among young consumers and did not contain any caffeine.“We welcome discussions with the F.D.A.” on industry changes necessary to protect consumers, a Prime representative added.But Dr. Bracho-Sanchez said the manner in which the companies were marketing the two beverages — with flashy packaging and a social media blitz pushed to younger consumers — made it difficult to tell them apart. The “energy” branding was also misleading, she added.“This is not true energy. This isn’t a good night’s sleep followed by a nutritious meal, this is a caffeine rush followed by a crash.”

Policy-makers are being urged to take notice of a University of Otago study that confirms that undertaking a short programme of high intensity interval training before surgery can substantially help with recovery.
The study, published in the journal Surgery, reviewed and analysed 12 studies including 832 patients who had undertaken preoperative high-intensity interval training. Such training involves repeated aerobic high-intensity intervals at about 80 per cent of the maximum heart rate followed by active recovery.
Lead investigator Dr Kari Clifford says the study included all types of major surgeries — those expected to last more than two hours or with an anticipated blood loss of greater than 500ml — and included liver, lung, colorectal, urologic and mixed major abdominal surgeries. The average age of participants in the intervention group was 66 and 67 in the control group.
“We have found that high intensity interval training (HIIT) is safe and effective for surgical patients. A HIIT program can meaningfully improve a patient’s fitness within four to six weeks, and this reduces postoperative complications and length of stay.”
The most significant result was the change in cardiorespiratory fitness (CRF) — a measure of how well the body takes in oxygen and delivers it to the muscles and organs during prolonged periods of exercise.
“The pooled results suggest that HIIT increases cardiorespiratory fitness by 2.39 ml/min/kg. This is not only significantly different than standard surgical care, but is also clinically relevant: we know that this level of increase is associated with a lower risk of adverse postoperative outcomes.”
Generally, post operative complications occur in about 30 per cent of patients, or up to 50 per cent for frail patients. In the study, those who undertook high intensity interval training prior to surgery, showed a consistent reduction in post-surgery complications, such as cardiac complications, pneumonia, and postoperative bowel issues, she says.
“Our study’s pooled results showed that HIIT reduces the risk of having a complication by 56 per cent, which is substantial; and on average they stayed for three fewer days in hospital.”
“All of these findings suggest that a period — even as brief as four weeks — of pre-surgery high intensity interval training may substantially improve patient outcomes and bring with it robust benefits across patient populations,” she says.
The next step is to find out how to implement such programmes.
“Supervised exercise programs can be expensive, so we are looking at how effective it is to support people training at home or in the community. Funding these programs may save money in the long term by reducing the cost of hospital stay and surgical complications.
“In the meantime, I would say to everyone, it is never too late to improve fitness, and this can really make a difference to health outcomes in the surgical context.”

New research has discovered neurons within the brain which detect and respond to changes in the level of sugar within the bloodstream.
Understanding how this blood-sugar detection system works and how these neurocircuits operate would give researchers and doctors greater insights into how our brains regulate our blood sugar and, perhaps, how to target them therapeutically to treat metabolic diseases like diabetes and obesity, according to the study authors.
The study was published June 22 online in Diabetes, a research journal of the American Diabetes Association.
“We’ve known for a long time that many neurons can detect sugar locally within the brain,” said Dr. Michael Schwartz, an endocrinologist with the University of Washington School of Medicine and co-director of the UW Medicine Diabetes Institute. “What is new, however, is the evidence that a subset of neurons located in the hypothalamus can sense and respond to sugar in the bloodstream itself, analogous to the cells in the pancreas that secrete insulin.”
In this study, researchers were able to monitor both blood-sugar levels and the activity of neurons within the hypothalamus of conscious mice in real time. They found that when blood sugar levels rise, the activity of this subset of neurons decreases rapidly. Researchers speculate that these neurons detect and respond to variation in blood sugar transmitted by sensory neurons that supply the vasculature (rather than sugar levels in the brain, which change much more slowly), Schwartz noted. This sensory information is then transmitted to one or more neurocircuits that control the blood sugar level in conjunction with the pancreas, which produces insulin for the body.
Clinically, this is important because when treating patients with diabetes, clinicians often find that the patients’ system is actively maintaining an elevated blood-sugar level, presumably “because that’s where the brain thinks the blood sugar level is supposed to be,” Schwartz said.
“For example, if a normal blood sugar is 100, a patient with diabetes may well have a blood sugar above 300,” he said. “If it’s been at that elevated level for days or weeks, and if you suddenly lower it back to 100, the brain will think that’s too low, and will try to increase blood-sugar level again.”
This evidence that diabetes is associated with an impaired ability of the brain to sense the blood-sugar level suggests that in the future, reversing this type of sensing defect may allow the brain to control blood sugar in a more appropriate way, Schwartz concluded.

The NewsHumans transmitted the coronavirus to white-tailed deer more than 100 times in late 2021 and early 2022, according to new research led by the U.S. Department of Agriculture’s Animal and Plant Health Inspection Service. The research also suggests that the virus probably spread widely among deer, that it mutated in the animals and that they may have passed these altered versions of the virus back to people at least three times.The findings, some of which were also published in the journal Nature Communications, add to concerns that deer, which are ubiquitous in the United States, might become a long-term animal reservoir for the virus and a potential source of new variants.“Deer regularly interact with humans and are commonly found in human environments — near our homes, pets, wastewater and trash,” Xiu-Feng Wan, an expert on zoonotic disease at the University of Missouri and an author of the new paper, said in a statement. “The potential for SARS-CoV-2, or any zoonotic disease, to persist and evolve in wildlife populations can pose unique public health risks.”Scientists collected more than 11,000 samples from deer in 26 states and Washington, D.C. They found that one-third had antibodies to the coronavirus and 12 percent were actively infected.Genna Martin/San Francisco Chronicle, via Associated PressWhy It Matters: Deer could be a source of new variants.There is no evidence that deer play a major role in spreading the virus to humans, but the transmission of the virus from people to animals raises several public health concerns.First, animal reservoir could allow viral variants that have disappeared from human populations to persist. Indeed, the new study confirms prior reports that some coronavirus variants, including Alpha and Gamma, continued to circulate in deer even after they became rare in people.New animal hosts also give the virus new opportunities to mutate and evolve, potentially giving rise to new variants that could infect people. If these variants are different enough from those that have previously circulated in humans, they could evade some of the immune system’s defenses.Background: Scientists have found signs of widespread infection in deer.Researchers at the Animal and Plant Health Inspection Service, in collaboration with other government and academic scientists, began looking for the coronavirus in free-ranging white-tailed deer in 2021, after studies suggested that the animals were susceptible to the virus.In that first year of surveillance work, the scientists ultimately collected more than 11,000 samples from deer in 26 states and Washington, D.C. Nearly a third of the animals had antibodies to the coronavirus, suggesting that they had previously been exposed, and 12 percent were actively infected, APHIS said on Tuesday.For the new Nature Communications paper, scientists from APHIS, the Centers from Disease Control and Prevention and the University of Missouri sequenced nearly 400 of the samples collected between November 2021 and April 2022. They found multiple versions of the virus in deer, including the Alpha, Gamma, Delta and Omicron variants.Then, the scientists compared the viral samples isolated from deer with those from human patients and mapped the evolutionary relationships between them. They concluded that the virus moved from humans to deer at least 109 times and that deer-to-deer transmission often followed.The virus also showed signs of adapting to deer, and the researchers identified several cases in North Carolina and Massachusetts in which humans were infected with these “deer-adapted” versions of the virus.What’s Next: Surveillance will continue.APHIS has expanded its surveillance to additional states and species.Many questions remain, including precisely how people are passing the virus to deer, and the role that the animals might play in sustaining the virus in the wild.