Publisher Health

Agent Orange, an herbicide used during the Vietnam War, is a known toxin with wide-ranging health effects. Even though Agent Orange has not been used for decades, there is increasing interest in its effects on the brain health of aging veterans. A new study by scientists at Brown University reveals the mechanisms by which Agent Orange affects the brain and how those processes can lead to neurodegenerative diseases.
The research shows that exposures to Agent Orange herbicidal chemicals damage frontal lobe brain tissue of laboratory rats with molecular and biochemical abnormalities that are similar to those found in early-stage Alzheimer’s disease. An early online version of this paper detailing the findings was published on Feb. 13 and is scheduled for publication in the Journal of Alzheimer’s Disease.
The findings could have important implications for military veterans who were exposed to Agent Orange during the Vietnam War, said study author Dr. Suzanne M. De La Monte, a Brown University physician-scientist.
“If we can show that prior exposure to Agent Orange leads to subsequent neurodegenerative disease, then that gives veterans a chance to get help,” De La Monte said.
But the study’s findings have much broader significance, she added, because the toxins in Agent Orange are also present in lawn fertilizers.
“These chemicals don’t just affect veterans; they affect our entire population,” said De La Monte, who is a professor of pathology and laboratory medicine and neurosurgery at Brown’s Warren Alpert Medical School.
Agent Orange is a synthetic defoliating herbicide that was widely used between 1965 and 1970 during the Vietnam War. Members of the U.S. military were exposed to the chemical when stationed close to enemy territory that had been sprayed by aircraft. Government reports show that exposure to Agent Orange also caused birth defects and developmental disabilities in babies born to Vietnamese women residing in the affected areas. Over time, studies showed that exposure to Agent Orange was associated with an increased risk of some cancers as well as cardiovascular disease and diabetes.

Research also revealed associations between Agent Orange exposures and later development of nervous system degenerative diseases, and significantly higher rates and earlier onsets of dementia. However, in the absence of a proven causal link between Agent Orange and aging-associated diseases, there has been a need for studies that improve understanding of the process by which the herbicide affects the brain.
“Scientists realized that Agent Orange was a neurotoxin with potential long-term effects, but those weren’t shown in a clear way,” De La Monte said. “That’s what we were able to show with this study.”
The analysis was conducted by De La Monte and Dr. Ming Tong, a research associate in medicine at Brown; both are also associated with Rhode Island Hospital, an affiliate of the Warren Alpert Medical School. Their research builds upon their recent studies of exposure to Agent Orange chemicals on immature human cells from the central nervous system showing that short-term exposure to Agent Orange has neurotoxic and early degenerative effects related to Alzheimer’s.
The researchers investigated the effects of the two main constituents of Agent Orange (2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid) on markers of Alzheimer’s neurodegeneration using the samples from the frontal lobes of laboratory rats. The mature, intact brain tissue samples included a full complex array of cell types and tissue structures.
The scientists treated the samples to cumulative exposure to Agent Orange, as well as to its separate chemical constituents, and observed the underlying mechanisms and molecular changes.
They found that treatment with Agent Orange and its constituents caused changes in the brain tissue corresponding to brain cell degeneration, and molecular and biochemical abnormalities indicative of cytotoxic injury, DNA damage and other issues.

The approach used by the researchers helped them better characterize the neuropathological, neurotoxic and neurodegenerative consequences of Agent Orange toxin exposures in young, otherwise healthy brains, as would have been the case for Vietnam War-era military personnel and many local residents in Vietnam.
“Looking for the early effects tells us that there is a problem that is going to cause trouble later on and also gives us a grip on the mechanism by which the agent is causing trouble,” De La Monte said. “So if you were going to intervene, you would know to focus on that early effect, monitor it and try to reverse it.”
Del La Monte hopes to be involved in additional research on human brain tissue to evaluate the long-term effects of Agent Orange exposures in relation to aging and progressive neurodegeneration in Vietnam War veterans.
The use of Agent Orange was prohibited by the U.S. government in 1971. However, the chemicals remain in the environment for decades, De La Monte said. According to the study authors, the widespread, uncontrolled use of Agent Orange in herbicide and pesticide products is such that one in three Americans has biomarker evidence of prior exposure.
Despite growing recognition of the broad toxic and carcinogenic effects of 2,4-dichlorophenoxyacetic acid, the researchers noted that concern has not achieved a level sufficient for federal agencies to ban its use. The researchers conclude that the results of this study and another recent publication support the notion that Agent Orange as well as its independent constituents (2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid) exert alarming adverse effects on the mature brain and central nervous system.
“That’s why it’s so important to look into the effects of these chemicals,” De La Monte said. “They are in the water; they are everywhere. We’ve all been exposed.”
This research was supported by the National Institute on Alcohol Abuse and Alcoholism at the National Institutes of Health (R01AA011431, R01AA028408).

What causes us to age? New “clocks” developed by researchers may help point to the answers. Investigators from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, unveil a new form of epigenetic clock — a machine learning model designed to predict biological age from DNA structure. The novel model distinguishes between genetic differences that slow and accelerate aging, predicts biological age and evaluates anti-aging interventions with increased accuracy. Results are published in Nature Aging.
“Previous clocks considered the relationship between methylation patterns and features we know are correlated with aging, but they don’t tell us which factors cause one’s body to age faster or slower. We have created the first clock to distinguish between cause and effect,” said corresponding author Vadim Gladyshev, PhD, a principal investigator in the Division of Genetics at BWH. “Our clocks distinguish between changes that accelerate and counteract aging to predict biological age and assess the efficacy of aging interventions.”
Aging researchers have long acknowledged the link between DNA methylation — alterations to our genetic structure that shape gene function — and its influence on the aging process. Notably, specific regions of our DNA, known as CpG sites, are more strongly associated with aging. While lifestyle choices, like smoking and diet, influence DNA methylation, so does our genetic inheritance, explaining why individuals with similar lifestyles may age at different rates.
Existing epigenetic clocks predict biological age (the actual age of our cells rather than chronological) using DNA methylation patterns. However, until now, no existing clocks have distinguished between methylation differences that cause biological aging and those simply correlated with the aging process.
Using a large genetic data set, first author Kejun (Albert) Ying, a graduate student in the Gladyshev lab, performed an epigenome-wide Mendelian Randomization (EWMR), a technique used to randomize data and establish causation between DNA structure and observable traits, on 20,509 CpG sites causal to eight aging-related characteristics. The eight aging-related traits included lifespan, extreme longevity (defined as survival beyond the 90th percentile), health span (age at first incidence of major age-related disease), frailty index (a measure of one’s frailty based on the accumulation of health deficits during their lifespan), self-rated health, and three broad aging-related measurements incorporating family history, socioeconomic status, and other health factors.
With these traits and their associated DNA sites in mind, Ying created three models, termed CausAge, a general clock that predicts biological age based on causal DNA factors, and DamAge and AdaptAge, which include only damaging or protective changes. Investigators then analyzed blood samples from 7,036 individuals ages 18 to 93 years old from the “Generation Scotland Cohort” and ultimately trained their model on data from 2,664 individuals in the cohort.
With these data, researchers developed a map pinpointing human CpG sites that cause biological aging. This map allows researchers to identify biomarkers causative to aging and evaluate how different interventions promote longevity or accelerate aging.

Scientists tested their clocks’ validity on data collected from 4,651 individuals in the Framingham Heart Study and the Normative Aging Study. They found that DamAge correlated with adverse outcomes, including mortality, and AdaptAge correlated with longevity, suggesting that age-related damage contributes to the risk of death while protective changes to DNA methylation may contribute to a longer lifespan.
Next, they tested the clocks’ ability to assess biological age by reprogramming stem cells (transforming specialized cells, like skin cells, back into a younger, less defined state where they can develop into various types of cells in the body). When applying the clocks to the newly transformed cells, DamAge decreased, indicating a reduction in age-related damage during reprogramming, while AdaptAge did not show a particular pattern.
Finally, the team tested their clocks’ performance in biological samples from patients with various chronic conditions, including cancer and hypertension, as well as samples damaged from lifestyle choices like smoking cigarettes. DamAge consistently increased in conditions associated with age-related damage, while AdaptAge decreased, effectively capturing protective adaptations.
“Aging is a complex process, and we still do not know what interventions against it actually work,” said Gladyshev. “Our findings present a step forward for aging research, allowing us to more accurately quantify biological age and evaluate the ability of novel aging interventions to increase longevity.”

Every year, around 50,000 people in the United States experience cardiogenic shock — a life-threatening condition, usually caused by a severe heart attack, in which the heart can’t pump enough blood for the body’s needs.
Many of these patients end up receiving help from a mechanical pump that can temporarily help the heart pump blood until it recovers enough to function on its own. However, in nearly half of these patients, the extra help leads to an imbalance between the left and right ventricles, which can pose danger to the patient.
In a new study, MIT researchers have discovered why that imbalance occurs, and identified factors that make it more likely. They also developed a test that doctors could use to determine whether this dysfunction will occur in a particular patient, which could give doctors more confidence when deciding whether to use these pumps, known as ventricular assist devices (VADs).
“As we improve the mechanistic understanding of how these technologies interact with the native physiology, we can improve device utility. And if we have more algorithms and metrics-based guidance, that will ease use for clinicians. This will both improve outcomes across these patients and increase use of these devices more broadly,” says Kimberly Lamberti, an MIT graduate student and the lead author of the study.
Elazer Edelman, the Edward J. Poitras Professor in Medical Engineering and Science and the director of MIT’s Institute for Medical Engineering and Science (IMES), is the senior author of the paper, which appears today in Science Translational Medicine. Steven Keller, an assistant professor of medicine at Johns Hopkins School of Medicine, is also an author of the paper.
Edelman notes that “the beauty of this study is that it uses pathophysiologic insight and advanced computational analyses to provide clinicians with straightforward guidelines as to how to deal with the exploding use of these valuable mechanical devices. We use these devices increasingly in our sickest patients and now have greater strategies as to how to optimize their utility.”
Imbalance in the heart
To treat patients who are experiencing cardiogenic shock, a percutaneous VAD can be inserted through the arteries until it is positioned across the aortic valve, where it helps to pump blood out of the left ventricle. The left ventricle is responsible for pumping blood to most of the organs of the body, while the right ventricle pumps blood to the lungs.

In most cases, the device may be removed after a week or so, once the heart is able to pump on its own. While effective for many patients, in some people the devices can disrupt the coordination and balance between the right and left ventricles, which contract and relax synchronously. Studies have found that this disruption occurs in up to 43 percent of patients who receive VADs.
“The left and right ventricles are highly coupled, so as the device disrupts flow through the system, that can unmask or induce right heart failure in many patients,” Lamberti says. “Across the field it’s well-known that this is a concern, but the mechanism that’s creating that is unclear, and there are limited metrics to predict which patients will experience it.”
In this study, the researchers wanted to figure out why this failure occurs, and come up with a way to help doctors predict whether it will happen for a given patient. If doctors knew that the right heart would also need support, they could implant another VAD that helps the right ventricle.
“What we were trying to do with this study was predict any issues earlier in the patient’s course, so that action can be taken before that extreme state of failure has been reached,” Lamberti says.
To do that, the researchers studied the devices in an animal model of heart failure. A VAD was implanted in the left ventricle of each animal, and the researchers analyzed several different metrics of heart function as the pumping speed of the device was increased and decreased.
The researchers found that the most important factor in how the right ventricle responded to VAD implantation was how well the pulmonary vascular system — the network of vessels that carries blood between the heart and lungs — adapted to changes in blood volume and flow induced by the VAD.

This system was best able to handle that extra flow if it could adjust its resistance (the slowing of steady blood flow through the vessels) and compliance (the slowing of large pulses of blood volume into the vessels).
“We found that in the healthy state, compliance and resistance could change pretty rapidly to accommodate the changes in volume due to the device. But with progressive disease, that ability to adapt becomes diminished,” Lamberti says.
A dynamic test
The researchers also showed that measuring this pulmonary vascular compliance and its adaptability could offer a way to predict how a patient will respond to left ventricle assistance. Using a dataset of eight patients who had received a left VAD, the researchers found that those measurements correlated with the right heart state, therefore predicting how well the patients adapted to the device, validating the findings from the animal study.
To do this test, doctors would need to implant the device as usual and then ramp up the speed while measuring the compliance of the pulmonary vascular system. The researchers determined a metric that can assess this compliance by using just the VAD itself and a pulmonary artery catheter that is commonly implanted in these patients.
“We created this way to dynamically test the system while simultaneously maintaining support of the heart,” Lamberti says. “Once the device is initiated, this quick test could be run, which would inform clinicians of whether the patient might need right heart support.”
The researchers now hope to expand these findings with additional animal studies and continue collaboration with manufacturers of these devices in the future, in hopes of running clinical studies to evaluate whether this test would provide information that would be valuable for doctors.
“Right now, there are few metrics being used to predict device tolerance. Device selection and decision-making is most often based on experiential evidence from the physicians at each institution. Having this understanding will hopefully allow physicians to determine which patients will be intolerant to device support and provide guidance for how to best treat each patient based on right heart state,” Lamberti says.
The research was funded by the National Heart, Lung and Blood Institute; the National Institute of General Medical Sciences; and Abiomed.

Chronic exposure of human skin to ultraviolet light causes premature aging, or photoaging. As the skin undergoes photoaging, type I collagen bundles, which are found in the dermis beneath the top layer of the skin and provide strength and support to skin, become fragmented. This leads to wrinkles, fragility and loss of support and elasticity.
“The best way to prevent damage to type I collagen by sunlight is to wear sunscreen consistently, daily if possible and particularly when spending time outdoors,” said Frank Wang, MD, the William B. Taylor Endowed Professor of Clinical Dermatology at U-M Medical School.
Experts observed in a new study that injection of the most popular type of dermal filler, cross-linked hyaluronic acid, into photoaged skin could reverse the dermal changes associated with photoaging.
These fillers are typically injected into the skin to reduce lines and wrinkles. They are thought to provide clinical improvement by adding volume to the skin, but researchers have found that cross-linked hyaluronic acid also stimulates production of new type I collagen in the dermis.
The filler does so rapidly, stimulating collagen production within several weeks of injection, and is long-lasting, promoting the accumulation of more collagen over the course of a year.
These findings indicate how the filler improves the appearance of skin in the short-term — a combination of space-filling and collagen. Additionally, since newly formed dermal collagen lasts many years, the findings also provide insight into how the filler can promote long-term clinical improvement, months or even a year after injection.
“A single injection of cross-linked hyaluronic acid dermal filler can lead to rapid and long-lasting improvement of skin by stimulating collagen deposition, and furthermore, repeat injections may add more collagen, eventually reducing the need for re-treatment,” Wang said.
Additional authors include Thy Thy Do, Noah Smith, Jeffrey S. Orringer, Sewon Kang, John J. Voorhees, and Gary J. Fisher, all of the U-M Department of Dermatology.
Funding/disclosures: Galderma donated cross-linked hyaluronic acid-containing syringes for research purposes but had no involvement in the design or conduct of the study or in the collection, management, analysis, and interpretation of the data. Galderma was not involved in the preparation or review of the manuscript. This study was supported by the University of Michigan Department of Dermatology Cosmetic Research Fund; and a Career Development Award from the Dermatology Foundation.

The F.T.C. and H.H.S. are examining the tactics of group purchasing organizations that generic industry executives say have led to scarce supplies of treatments like chemotherapy.The Federal Trade Commission and the Department of Health and Human Services said on Wednesday that they would examine the causes of generic drug shortages and the practices of “powerful middlemen” that are involved in the supply chain.The federal agencies’ inquiry is aimed at the group purchasing organizations and drug distributors that have been in the spotlight in recent months as drug shortages reached a 10-year peak. The agencies want to examine the companies’ influence on how the drugs are sold to hospitals and other health facilities, assessing whether the middlemen put pressure on pricing and manufacturing that led to breakdowns.During Congressional hearings in the last year, oncology experts have testified about the effects of the shortages, describing difficult decisions that forced them to ration key chemotherapy drugs. They detailed month-to-month, sometimes week-to-week, gaps in supplies that were posing deadly risks for some patients.“For years Americans have faced acute shortages of critical drugs, from chemotherapy to antibiotics, endangering patients,” Lina Khan, the F.T.C. chairwoman, said in a statement. “Our inquiry requests information on the factors driving these shortages and scrutinizes the practices of opaque drug middlemen.”In earlier interviews with The Times, generic drug industry executives had expressed deepening concerns about their reliance on three major group purchasing organizations for contracts to sell medicines to hospitals and health center customers. The generic executives complained that their companies sometimes offered below-market prices to get big contracts, a strategy that had eroded stability in the industry, especially among makers of sterile injectable products often used in surgical and cancer care.Lawmakers have echoed the concerns. Late last year, Senator Ron Wyden, a Democrat of Oregon and chairman of the Senate Finance Committee, criticized “very powerful health care middlemen” in the generic drug industry. Last month, he and Senator Mike Crapo, a Republican of Idaho, outlined ways to limit drug shortages, focusing in part on proposed changes to Medicare payments for sterile injectable drugs.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.

Human cases are rare in the United States, but in some Western areas cats that hunt rodents can become infected — and even pass on the disease to their owners.Officials in Deschutes County, Ore., announced last week that a local resident had been diagnosed with the plague — and that the resident had probably been infected by a pet cat.The cat, which was symptomatic, died from the infection, but the human patient is currently recovering, said Emily Horton, a public health program manager for the county. No additional cases have been identified, officials said.Although the plague is best known for killing tens of millions of people in medieval Europe, the bacterium that causes the disease still circulates. It is common in some wild rodent populations in the western United States.“A lot of people are not aware that plague is endemic in parts of the U.S.,” said Dr. Erin Phipps, New Mexico’s state public health veterinarian. “It’s not a disease of the past.”Human cases are rare and treatable when caught early. But the Oregon case is a reminder that cat owners and veterinarians in plague-prone places should remain alert to the risks of infection, said Dr. Sarah Lathrop, a veterinarian and epidemiologist at the University of New Mexico. “If you have a pet cat in that area that hunts outside, it has to be on your radar,” she said.Here’s what to know:Scanning electron micrograph image of Yersinia pestis bacteria in the gut of a flea.NIAID/Science SourceWe 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.

A research team led by the University of California, Irvine has created 20 new recombinant rabies viral vectors for neural circuit mapping that offer a range of significant advantages over existing tools, including the ability to detect microstructural changes in models of aging and Alzheimer’s disease brain neurons.
The study published today online in the journal Molecular Psychiatry, introduced proof-of-concept data demonstrating the power of these new vectors, which express a range of improved fluorescent proteins to provide expanded multi-scale multi-modal capabilities. Naturally occurring rabies infections target the nervous system. Scientists harnessed this tendency to create engineered forms of the rabies virus that are coupled to sensors and other payloads — for example, some respond to light by turning bright green and act as tracers that map brain circuits.
“Viral genetic tools are critical for improving anatomical mapping and functional studies of cell-type-specific and circuit-specific neural networks,” said Xiangmin Xu, co-corresponding author and UCI Chancellor’s Professor of anatomy & neurobiology and director of the Center for Neural Circuit Mapping. “These new variants significantly enhance the capability and reach of neural labeling and circuit mapping across microscopic and macroscopic imaging scales and modalities, including 3D light and X-ray microscopy. We will make these new tools readily available to the neuroscience community through our established service platform at the CNCM.”
These new recombinant viral vectors are designed to target very specific components of neuron biology in order to analyze pathological changes that occur during Alzheimer’s disease and other brain diseases. They can be targeted to specific sub-cellular locations and organelles, as well as live imaging of neuronal activities using calcium indicators. The team conducted imaging analysis of mouse brains to demonstrate the discovery power of these new tools.
“These cutting-edge tools hold immense potential for understanding neural circuitry in both normal and pathological conditions and offer the ability to target specific regions of the brain with precision peptides or proteins to modulate neuronal functions for targeted treatment strategies,” said Bert Semler, co-corresponding author and UCI Distinguished Professor of Microbiology & Molecular Genetics.
Alexis Bouin, Ph.D. and Ginny Wu are co-first authors who led and coordinated the project. Additional team members include Orkide Koyuncu, assistant professor of microbiology & molecular genetics; Qiao Ye, graduate student; Michele Wu, Liqi Tong, Ph.D., and Lujia Chen, Ph.D., members of the Xu lab, and Todd Holmes, professor of physiology & biophysics. Leveraging the UCI Center for Neural Circuit Mapping’s broad collaborative network, team members from UCSD include Keun-Young Kim, Sebastien Phan, Mason R. Mackey, Ranjan Ramachandra,and Distinguished Professor Mark H. Ellisman.
This work was supported by National Institutes of Health grants RF1MH120020, R01FD007478, R35GM127102, R24GM137200, U24NS120055, and R01DA038896; and National Science Foundation grant NSF2014865-UTA20-00890.

Canadian researchers led by Montreal radiologist Gilles Soulez have developed a novel approach to treat liver tumours using magnet-guided microrobots in an MRI device.
The idea of injecting microscopic robots into the bloodstream to heal the human body is not new. It’s also not science fiction.
Guided by an external magnetic field, miniature biocompatible robots, made of magnetizable iron oxide nanoparticles, can theoretically provide medical treatment in a very targeted manner.
Until now, there has been a technical obstacle: the force of gravity of these microrobots exceeds that of the magnetic force, which limits their guidance when the tumour is located higher than the injection site.
While the magnetic field of the MRI is high, the magnetic gradients used for navigation and to generate MRI images are weaker.
“To solve this problem, we developed an algorithm that determines the position that the patient’s body should be in for a clinical MRI to take advantage of gravity and combine it with the magnetic navigation force,” said Dr. Gilles Soulez, a researcher at the CHUM Research Centre and director of the radiology, radio-oncology and nuclear medicine department at Université de Montréal.
“This combined effect makes it easier for the microrobots to travel to the arterial branches which feed the tumour,” he said. “By varying the direction of the magnetic field, we can accurately guide them to sites to be treated and thus preserve the healthy cells.”
Toward greater precision

Published in Science Robotics, this proof of concept could change the interventional radiology approaches used to treat liver cancers.
The most common of these, hepatocellular carcinoma, is responsible for 700,000 deaths per year worldwide, and is currently most often treated with transarterial chemoembolization.
Requiring highly qualified personnel, this invasive treatment involves administering chemotherapy directly into the artery feeding the liver tumour and blocking the blood supply to the tumour using microcatheters guided by X-ray.
“Our magnetic resonance navigation approach can be done using an implantable catheter like those used in chemotherapy,” said Soulez. “The other advantage is that the tumours are better visualized on MRI than on X-rays.”
For this study, Soulez and his research team collaborated with those of Sylvain Martel (Polytechnique Montreal) and Urs O. Häfeli’s (University of British Columbia). The study’s first author, Ning Li, is a postdoctoral fellow in Dr. Soulez’s laboratory.
Thanks to the development of an MRI-compatible microrobot injector, the scientists were able to assemble “particle trains,” aggregates of magnetizable microrobots. As these have a greater magnetic force, they are easier to pilot and detect on the images provided by the MRI device.

In this way, the scientists can ensure not only that the train is going in the right direction, but also that the treatment dose is adequate. Over time, each microrobot will carry a portion of the treatment to be delivered, so it’s essential that radiologists know how many there are.
A good sense of direction
“We carried out trials on twelve pigs in order to replicate, as closely as possible, the patient’s anatomical conditions,” said Soulez. “This proved conclusive: the microrobots preferentially navigated the branches of the hepatic artery which were targeted by the algorithm and reached their destination.”
His team made sure that the location of the tumour in different parts of the liver did not influence the effectiveness of such an approach.
“Using an anatomical atlas of human livers, we were able to simulate the piloting of microrobots on 19 patients treated with transarterial chemoembolization,” he said. “They had a total of thirty tumours in different locations in their livers. In more than 95 per cent of cases, the location of the tumour was compatible with the navigation algorithm to reach the targeted tumour.”
Despite this scientific progress, clinical application of this technology is still a long way off.
“First of all, using artificial intelligence, we need to optimize real-time navigation of the microrobots by detecting their location in the liver and also the occurrence of blockages in the hepatic artery branches feeding the tumour,” said Soulez.
Scientists will also need to model blood flow, patient positioning and magnetic field direction using software that simulates the flow of fluids through the vessels. This will make it possible to assess the impact of these parameters on the transport of the microrobots to the target tumour, thus improving the accuracy of the approach.

More than one hundred key genes linked to DNA damage have been uncovered through systematic screening of nearly 1,000 genetically modified mouse lines, in a new study published today (14 February) in Nature.
The work provides insights into cancer progression and neurodegenerative diseases as well as a potential therapeutic avenue in the form of a protein inhibitor.
The genome contains all the genes and genetic material within an organism’s cells. When the genome is stable, cells can accurately replicate and divide, passing on correct genetic information to the next generation of cells. Despite its significance, little is understood about the genetic factors governing genome stability, protection, repair, and the prevention of DNA damage1.
In this new study, researchers from the Wellcome Sanger Institute, and their collaborators at the UK Dementia Research Institute at the University of Cambridge, set out to better understand the biology of cellular health and identify genes key to maintaining genome stability.
Using a set of genetically modified mouse lines, the team identified 145 genes that play key roles in either increasing or decreasing the formation of abnormal micronuclei structures2. These structures indicate genomic instability and DNA damage, and are common hallmarks of ageing and diseases.
The most dramatic increases in genomic instability were seen when the researchers knocked out the gene DSCC1, increasing abnormal micronuclei formation five-fold. Mice lacking this gene mirrored characteristics akin to human patients with cohesinopathy disorders3, further emphasising the relevance of this research to human health.
Using CRISPR screening, researchers showed this effect triggered by DSCC1 loss could be partially reversed through inhibiting protein SIRT14. This offers a highly promising avenue for the development of new therapies.

The findings help shed light on genetic factors influencing the health of human genomes over a lifespan and disease development.
Professor Gabriel Balmus, senior author of the study at the UK Dementia Research Institute at the University of Cambridge, formerly at the Wellcome Sanger Institute, said: “Continued exploration on genomic instability is vital to develop tailored treatments that tackle the root genetic causes, with the goal of improving outcomes and the overall quality of life for individuals across various conditions. Our study underscores the potential of SIRT inhibitors as a therapeutic pathway for cohesinopathies and other genomic disorders. It suggests that early intervention, specifically targeting SIRT1, could help mitigate the biological changes linked to genomic instability before they progress.”
Dr David Adams, first author of the study at the Wellcome Sanger Institute, said: “Genomic stability is central to the health of cells, influencing a spectrum of diseases from cancer to neurodegeneration, yet this has been a relatively underexplored area of research. This work, of 15 years in the making, exemplifies what can be learned from large-scale, unbiased genetic screening. The 145 identified genes, especially those tied to human disease, offer promising targets for developing new therapies for genome instability-driven diseases like cancer and neurodevelopmental disorders.”
Notes: Various sources of damage to the genome can include radiation, chemical exposure, and errors during DNA replication or repair processes. Micronuclei are small abnormal structures, often referred to as “mutation factories,” containing misplaced genetic material, that should otherwise be in the cell nucleus. Their presence signifies an increased risk of diseases like cancer and developmental disorders. Cohesinopathy disorders are a group of genetic conditions resulting from dysfunctional cohesin proteins, essential for proper chromosome organisation and segregation during cell division. This can lead to a spectrum of developmental abnormalities, intellectual disability, distinctive facial features and growth retardation. When the SIRT1 protein was suppressed, DNA damage reduced and they could rescue the negative effects of DSCC1 loss associated with cohesion disruption. This action was via restoring chemical levels of a protein called SMC3.

Significantly more babies were born on a weekday instead of weekend day or holiday, reveals a large-scale analysis of 21 million births in Japan over almost four decades published February 14, 2024 in the open-access journal PLOS ONE by Miho Sassa from the University of Tokyo, Japan, and colleagues.
Medical resources are generally stretched during holidays (including weekends) due to factors like staffing and hospital policies. This may amplify holiday effects: disparities and variations of health outcomes between holidays and weekdays. Dr. Sassa and colleagues studied this holiday effect with a focus on birth, especially high-risk births as measured by babies born preterm and/or with a low birthweight.
The authors used birth certificate data from over 21 million individuals born from 1979-2018 (which included birthday, birthweight, and gestational age) to categorize individuals into five groups: low birthweight (