Photo by Kampus Production: https://www.pexels.com/photo/man-in-blue-and-black-crew-neck-shirt-8638036/
A new study has shown how muscle stem cells protect themselves from loss in old age: as we age, muscles lose their ability to regenerate quickly, due to increased production of the protein NDRG1 in muscle stem cells. Prof Dr Julia von Maltzahn from the BTU Cottbus-Senftenberg, who has spent many years researching muscle regeneration during ageing as a group leader at the Leibniz Institute on Aging – Fritz Lipmann Institute (FLI), has published a commentary on this article, as these new findings will change the way we look at changes in stem cells during ageing.
Muscle stem cells are essential for repairing our skeletal muscles. In young people, they respond very quickly to injuries, dividing and helping to rapidly replace damaged muscle tissue. However, these cells change with age, and muscles regenerate much more slowly – this has been known for some time.
A study on “Cellular survivorship bias as a mechanistic driver of muscle stem cell aging” by Jengmin Kang et al. from Stanford University School of Medicine, USA, now published in the journal Science, reveals for the first time an important mechanism behind the changes in muscle stem cells during aging. In aging muscle stem cells in mice, the protein NDRG1 is produced in increased amounts, which slows down their activation after injuries but at the same time increases their survivability. This balance of delayed activity during regeneration and increased resistance explains a fundamental trade-off in the aging process of muscle regeneration – and provides a new cellular mechanism behind the observed loss of function of aging cells.
Prof Dr Julia von Maltzahn classifies the new findings by Kang et al. against the background of relevant work on changes in muscle stem cells associated with aging as follows.
“The study shows that muscle stem cells develop a kind of protective mechanism during the aging process that leads to the survival of a subpopulation of stem cells. It is therefore important to look at the aging process and not the final stage.”
Newborns listening to Bach music predicted rhythm, but not melody, according to their brain waves
Human newborns can predict rhythmic structure from music, while they are not as good at expecting melodic changes. Image credit: Diego Perez-Lopez, PLOS, CC-BY 4.0
Babies are born with the ability to predict rhythm, according to a study published February 5th in the open-access journal PLOS Biology by Roberta Bianco from the Italian Institute of Technology, and colleagues.
It’s anticipating a beat drop, key change or chorus in a song you’ve never heard. Across all cultures, humans can inherently anticipate rhythm and melody. But are babies born with these behaviours, or are they learned? Research shows that by approximately 35 weeks of gestation, foetuses begin to respond to music with changes in heart rate and body movements. However, newborns’ ability to anticipate rhythm and melody is not fully understood.
To understand babies’ musical aptitudes, researchers played J.S. Bach’s piano compositions for an audience of 49 sleeping newborns. Musical stylings included 10 original melodies and four shuffled songs with scrambled melodies and pitches. While the babies listened, the researchers used electroencephalography – electrodes placed on the babies’ heads – to measure their brainwaves. When the babies’ brain waves showed signs of surprise, it meant they expected the song to go one way, but it went another.
The newborns tended to show neural signs of surprise when the rhythm unexpectedly changed; in other words, the miniature maestros had generated musical expectations based on rhythm. Previously, this result had been observed in non-human primates. The researchers found no evidence that the newborns tracked melody or were surprised by unexpected melodic changes, a skill that comes at an unknown exact point later in development.
According to the authors, understanding how humans become aware of rhythm can help biologists understand how our auditory systems develop. Future studies can investigate how exposure to music during gestation affects acquisition of rhythm and melody.
The authors add, “Are newborns ready for Bach? Newborns come into the world already tuned in to rhythm. Our latest research shows that even our tiniest 2-day old listeners can anticipate rhythmic patterns, revealing that some key elements of musical perception are wired from birth. But there’s a twist: melodic expectations – our ability to predict the flow of a tune – don’t seem to be present yet. This suggests that melody isn’t innate but gradually learned through exposure. In other words, rhythm may be part of our biological toolkit, while melody is something we grow into.”
Study finds genetic contribution to human lifespan is about 50% – more than double previous estimates
Photo by Matteo Vistocco on Unsplash
What determines how long we live – and to what extent is our lifespan shaped by our genes? Surprisingly, scientists believed for decades that the heritability of human lifespan was relatively low compared to other human traits, standing at just 20 to 25%; some recent large-scale studies even placed it below 10%. Now, a new study from the Weizmann Institute of Science, published in Science, presents an entirely different picture. According to the findings, genetics accounts for about 50% of variation in human lifespan – twice as much, or more, than previously thought.
The study was led by Ben Shenhar from the lab of Prof Uri Alon of Weizmann’s Molecular Cell Biology Department.
“For many years, lifespan was attributed mainly to non-genetic factors, fuelling scepticism about genetic determinants of longevity”
Using mathematical models and analyses of three large twin databases from Sweden and Denmark – including, for the first time in this context, a dataset of twins who were raised apart – the researchers showed that earlier heritability estimates were masked by high levels of extrinsic mortality, such as deaths caused by accidents, infections and environmental hazards. Filtering out such extrinsic factors was impossible in historic datasets because they provided no information about the cause of death. To compensate for this limitation, the researchers developed an innovative framework that included mathematical simulation of virtual twins to separate deaths due to biological ageing from those caused by extrinsic factors. The new results are consistent with the heritability of other complex human traits and with findings from animal models.
Science Numbers
Up to age 80, the risk of dying from dementia shows a heritability of about 70% – far higher than that of cancer or heart disease.
The results have far-reaching implications for ageing research and public health. “For many years, human lifespan was thought to be shaped almost entirely by non-genetic factors, which led to considerable scepticism about the role of genetics in ageing and about the feasibility of identifying genetic determinants of longevity,” says Shenhar. “By contrast, if heritability is high, as we have shown, this creates an incentive to search for gene variants that extend lifespan, in order to understand the biology of ageing and, potentially, to address it therapeutically.”
One- and three-month regimens both had few adverse reactions and high rates of completion
Tuberculosis bacteria. Credit: CDC
A study comparing one- and three-month antibiotic treatments to prevent active tuberculosis (TB) finds that a high percentage of patients successfully completed both regimens and suffered few adverse side effects. A team led by Richard Chaisson, of the Johns Hopkins School of Medicine, reports these findings February 10th in the open access journal PLOS Medicine.
Following TB exposure, the World Health Organization has traditionally recommended six to nine months of antibiotic treatment to prevent an active infection from developing, but many individuals fail to complete the long course of medication. Studies have shown that shorter regimens lasting one and three months are effective at preventing TB, but the one-month treatment had only been tested in people living with HIV, and the safety of the two regimens had not been compared in a head-to-head trial.
Researchers performed a clinical trial in 500 people residing in Brazil, who were not living with HIV and had been exposed to TB. They randomly assigned participants to take two antibiotics, isoniazid and rifapentine, daily for one month, or weekly for three months. Both the one- and three-month regimens had similarly high rates of completion, at 89.6% and 84.1%, respectively. Adverse reactions were typically mild or moderate, and occurred at comparable rates in both groups. Both regimens were deemed successful and neither proved superior to the other.
Expanding the number of people who receive preventive therapy is essential for reducing TB infections globally, but these efforts have been hampered by several factors, including the length of the treatments. The new findings provide evidence that a one-month course of antibiotics is safe for patients, regardless of HIV status, and will help clinicians, public health programs, and patients to make informed choices about which regimens to use. Experts hope the success of shorter treatments, combined with the availability of newer generic formulations of the medications, which can be taken at home, will facilitate broader use of preventive therapy for TB.
The authors add, “Prevention of tuberculosis in people at the greatest risk is essential for global control of the disease, and shorter preventive treatment regimens will be instrumental in catalyzing uptake in high-burden countries.”
“Tuberculosis preventive treatment regimens have now been shortened from 6-9 months of daily medication to 1 month of daily treatment or 12 once-weekly doses, a transformational advance. Our study shows that both of the ultra-short regimens are well-tolerated and have high rates of completion.”
“The high rates of treatment completion and excellent safety profile of the short-course regimens will help Brazil and other high-burden countries achieve TB control by facilitating widespread uptake of TB preventive treatment,” states coauthor Betina Durovni.
“Preventing TB with short courses of well-tolerated medicines ensures that millions more people around the world can be protected from the devastating consequences of TB disease,” says coauthor Marcelo Cordeiro-Santos.
Discovery could lead to mRNA therapeutic to reduce the risk of cardiac damage
Graphical Abstract summarising the key findings of the paper. The authors found that severe influenza damages the heart by exploiting a specific immune cells and engaging a type-I interferon response. The authors also show that therapeutic silencing of the response mitigates heart damage.
Researchers at Mount Sinai in the US have identified a cellular mechanism linking infections from influenza A viruses (IAVs) to cardiovascular disease, providing critical insights on how influenza can damage the heart and increase the risk of a heart attack or other major cardiovascular event.
Through its work with mouse models and human data, the team also provided evidence that a cutting-edge modified mRNA treatment that dampens an interferon signalling pathway in the heart can significantly mitigate cardiac damage following viral infection while preserving the protective antiviral response of the immune system. The study was published in the February 9 issue of Immunity.
“We have known for years that the frequency of heart attacks increases during flu season, yet outside of clinical intuition, scant evidence exists of the underlying mechanisms of that phenomenon,” says senior author Filip Swirski, PhD, Director of the Cardiovascular Research Institute at the Icahn School of Medicine at Mount Sinai.
“Studies like ours are now shedding valuable light on immune system pathways, like the antiviral cytokine type 1 interferon (IFN-1), that factor into damage to the heart following severe influenza infection. These findings offer great promise for the development of new therapies, which are desperately needed since there are currently no viable clinical options to prevent cardiac damage.”
Influenza A viruses are responsible for an estimated 1 billion infections globally each year, ranging from seasonal flu outbreaks locally to pandemics globally. While most infections are mild and self-resolving, in some cases they can become severe or even fatal, particularly when the virus travels to the heart and triggers the death of cardiomyocytes, specialized muscle cells that are responsible for the rhythmic contraction and relaxation of the heart.
The Mount Sinai team studied autopsies of 35 hospitalised patients who died of influenza and found that more than 85% had at least one significant cardiovascular comorbidity, such as hypertension, and that the majority had multiple comorbidities, including atherosclerosis and cardiac fibrosis, underscoring cardiovascular disease as a major driver of influenza mortality.
The research team also uncovered the mechanism by which cardiac damage occurs. They learned, for example, that a novel subset of white blood cells, known as pro-dendritic cell 3, becomes infected in the lung and, after traveling to the heart, produces large amounts of type 1 interferon. This, instead of fulfilling its mission of clearing the virus from the heart, triggers the death of cardiomyocytes, impairing cardiac output.
“We found that the pro-dendritic cell 3 acts as the ‘Trojan horse’ of the immune system during influenza infection, becoming infected in the lung, trafficking the virus to the heart, and disseminating it to cardiomyocytes. This process causes production of the damaging type 1 interferon that comes with considerable collateral damage to the heart,” explains Jeffrey Downey, PhD, a member of Dr Swirski’s laboratory who served as lead author of the study. “The hopeful news for patients is that by injecting a novel mod-RNA therapeutic that modulates the IFN-1 signaling pathway, we reduced levels of cardiac damage, as evidenced by lower troponin, and improved cardiac function, as measured by higher left ventricular ejection fraction.”
As part of its ongoing research, Dr Swirski’s team is collaborating with Lior Zangi, PhD, Associate Professor of Medicine (Cardiology), and Genetics and Genomic Sciences, at the Icahn school of Medicine at Mount Sinai, to investigate the use of a safe and effective systemic delivery method of the mod-RNA therapeutic to the heart’s muscle cells, instead of the direct injection method used in its proof-of-concept study. Additional work is focused on the pro-dendritic cell 3 itself: why is it so susceptible to influenza and how could its protective capacity be fully harnessed to potentially minimize heart damage exacerbated by cardiovascular disease?
“Pathogens are constantly emerging and evolving, which means our strategies to combat them must evolve as well,” says Dr Swirski. “Better understanding of influenza pathogenesis and immune pathways that are activated throughout the body will help fuel the next stage of advanced care.”
Researchers at the Icahn School of Medicine at Mount Sinai, in collaboration with other leading institutions across the country, have published an innovative study that provides radiation oncologists with practical guidance to identify and protect female sexual organs during pelvic cancer treatment.
Published in the latest issue of Practical Radiation Oncology, this study addresses a long-standing gap in cancer care by bringing key female sexual anatomy into consideration during routine radiotherapy planning and survivorship research.
The study, “Getting c-literate: Bulboclitoris functional anatomy and its implications for radiotherapy,” synthesises current scientific knowledge and pairs it with original anatomic dissection, histology, and advanced imaging analysis. The work focuses on the bulboclitoris, a female erectile organ (consisting of the clitoris and the vestibular bulbs) that plays a central role in sexual arousal and orgasm and can be exposed to radiation during treatment for pelvic cancers.
“Pelvic radiotherapy can be life-saving, but it can also affect sexual function and quality of life,” said Deborah Marshall, MD, MAS, Assistant Professor, Departments of Radiation Oncology and Population Health Science and Policy at the Icahn School of Medicine at Mount Sinai; Division Chief of Women’s Health, Department of Population Health Science and Policy; and senior author of the study. “Compared to male sexual anatomy, female erectile structures have been largely invisible in standard radiation workflows. Our goal was to provide clinicians with a practical anatomy-grounded way to change that.”
Using detailed anatomic and radiologic correlation, the research team demonstrates how the bulboclitoris and related neurovascular structures can be identified on standard CT and MRI scans and consistently outlined (or “contoured”) for radiotherapy planning. This step-by-step guidance makes it feasible for clinicians to measure radiation dose to these tissues and begin linking exposure to patient-reported outcomes related to arousal and orgasm.
“This work builds upon our previous knowledge that the clitoris is not just an external structure,” Dr. Marshall said. “It includes an entire internal organ comprised of erectile tissues located just outside the pelvis, and those tissues matter for sexual health and, in particular, for female sexual pleasure. Once clinicians can reliably see and measure them, we can begin to ask better questions, have better conversations with patients, and ultimately deliver better care.”
Sexual function outcomes after pelvic radiotherapy have historically been understudied in women, limiting counselling, toxicity prevention strategies, and equitable survivorship care. By establishing a shared, standardised approach to identifying the bulboclitoris, the study lays the groundwork for future research to develop dose-volume constraints and mitigation strategies, as other organs at risk are managed in radiation oncology.
For clinicians, the framework enables routine contouring and dose reporting using CT alone when necessary, with MRI improving soft-tissue visualization when available. In the absence of prospective dose-response data, the authors recommend minimising radiation dose to the bulboclitoris when oncologically appropriate, using an “as low as reasonably achievable” approach.
For patients, the work supports more informed conversations about potential sexual side effects of pelvic radiotherapy, including changes in arousal, sensation, orgasm, lubrication, or pain. This research also promotes more personalized treatment planning that considers female sexual health and pleasure as a legitimate and important component of cancer survivorship.
Next steps include prospective research through Mount Sinai’s STAR program, deeper mapping of neurovascular anatomy relevant to sexual function, expanded educational resources for oncology and radiology teams, and improved patient-reported outcome measures that reflect diverse sexual practices and experiences.
Gliobastoma (astrocytoma) WHO grade IV – MRI sagittal view, post contrast. 15 year old boy. Credit: Christaras A.
The brain and spinal cord is made up of billions of neurons connected by synapses and managed and modified by glial cells. When neurons die, this communication network is disrupted and since this loss is irreversible, neuron death causes sensory loss, motor impairment and cognitive decline.
An interdisciplinary team of researchers from the University of Notre Dame is investigating the mechanisms of neuron death caused by chronic compression – such as the pressure exerted by a brain tumour – to better understand how to prevent neuron loss.
Published in the Proceedings of the National Academy of Sciences, their study found that chronic compression triggers neuron death by a variety of mechanisms, both directly and indirectly. The research is helping lay the groundwork for identifying therapies to prevent indirect neuron death.
“The impetus for this project was to figure out those underlying mechanisms. In cancer research, most researchers are focused on the tumour itself, but in the meantime, while the tumour is sitting there and growing, it’s damaging the organ that it’s living in,” said Meenal Datta, the Jane Scoelch DeFlorio Collegiate Professor of Aerospace and Mechanical Engineering at Notre Dame and co-lead author of the study. “We fully believe that these growth-induced mechanical forces of the tumor as it expands is part of the reason we see damage in the brain.”
As an engineer who leads the TIME Lab, Datta studies the mechanics of tumors and the microenvironment, specifically for glioblastoma, an incurable brain cancer. She had found in prior work that tumors damage the surrounding brain. But to understand the mechanisms by which tumors kill neurons from compression alone, Datta needed a “hardcore neuroscientist.”
Imaging of neurons from an experiment with the control group neurons on the left and the neurons impact by chronic compression on the right. (Provided by the Patzke lab.)
That neuroscientist is Christopher Patzke, the John M. and Mary Jo Boler Assistant Professor in the Department of Biological Sciences at Notre Dame and co-lead author of the study. Patzke utilises induced pluripotent stem cells (iPSCs), which are either obtained from external sources or generated directly in his lab. These cells function like embryonic stem cells and can be differentiated or changed in the lab into any cell type in the body, including neurons.
For this study, iPSCs were used to create neural cells and develop a model system of neurons and glial cells that behave as a neuronal network would in the brain. Researchers grew the cells and then applied pressure to the system to mimic the chronic compression of a glioblastoma tumour.
After compressing the cells, graduate students Maksym Zarodniuk and Anna Wenninger, from Datta and Patzke’s labs respectively, compared how many neurons and glial cells died versus lived.
“For the neurons that are still alive, many of them have this programmed self-destruction signaling activated,” Patzke said. “We wanted to understand which molecular pathway was responsible for this; is there a way to save neurons from going down the drain to this cell death mechanism?”
By sequencing and analysing all messenger RNA from the living neuronal and glial cells, the researchers found an increase in HIF-1 molecules, signalling for stress adaptive genes to improve cell survival, which leads to inflammation in the brain. The compression also triggered AP-1 gene expression, a type of neuroinflammatory response.
Both neurological reactions are indicators that neuronal damage and death is underway.
An analysis of data from the Ivy Glioblastoma Atlas Project shows that glioblastoma patients also reflect these compressive stress patterns and gene expression changes as well as synaptic dysfunction in line with the experiment’s results. The researchers confirmed these results by mimicking force via a live compression system applied to preclinical models of brains.
Overall, the findings may help explain why glioblastoma patients experience cognitive impairments, motor deficits and elevated seizure risk. Additionally, the signalling pathways offer opportunities for researchers to explore as drug targets to reduce neuronal death.
“Our approach to this study was disease agnostic, so our research could potentially extend to other brain pathologies that affect mechanical forces in the brain such as traumatic brain injury,” Datta said. “I’m all in on mechanics. Whatever it is that you’re interested in when it comes to cancer, above your question of interest, mechanics is sitting there and many don’t even know they should be considering it.”
The mechanics of compression and its effect on neuron loss is key for future research.
“Understanding why neurons are so vulnerable and die upon compression is critical to prevent excessive sensory loss, motor impairment and cognitive decline,” Patzke said. “This is how we will help patients.”
Just over one in 10 deaths from a wide range of infectious diseases are associated with obesity worldwide, finds a major new study led by a UCL researcher.
People with obesity face a 70% higher risk of hospitalisation or death from an infection than those of a healthy weight, suggest the findings published in The Lancet.
Obesity is linked to an increase in the risk posed by many different infectious diseases, from flu and COVID to stomach bugs and urinary tract infections, and the researchers found that the higher the BMI, the greater the risk.
The study’s lead author, Professor Mika Kivimaki (UCL Faculty of Brain Sciences), said: “Obesity is well known as a risk factor for metabolic syndrome, diabetes, cardiovascular disease, and many other chronic conditions. Here we have found robust evidence that obesity is also linked to worse outcomes from infectious diseases, as becoming very ill from an infection is markedly more common among people with obesity.”
The researchers studied data from over 540 000 people who participate in large cohort studies in the UK (the UK Biobank dataset) and Finland, to look at the relationship between obesity and severe infectious disease. Participants had their body mass index (BMI) assessed when they entered the studies and were then followed up for an average of 13-14 years.
The researchers found that people with obesity (defined as a BMI of 30 or higher) had a 70% higher risk of hospitalisation or death from any infectious disease in the study period compared to people with a BMI between 18.5 to 24.9 (classified as a healthy weight).
The risk increased steadily as body weight increased. People with a BMI of 40 or higher had three times the severe infection risk compared to people with a healthy weight.
The link between obesity and severe infections was consistent regardless of the measure of obesity used (BMI, waist circumference, or waist-to-height ratio, where data was available) and for a wide range of infection types.
The study included data on 925 bacterial, viral, parasitic, and fungal infectious diseases, and the authors also honed in on 10 common infectious diseases in more detail. For most of these diseases, including flu, Covid-19, pneumonia, gastroenteritis, urinary tract infections, and lower respiratory tract infections, they found that people with obesity were more likely to be hospitalised or die than people with a healthy BMI. However, obesity did not appear to increase the risk of severe HIV or tuberculosis.
The analysis found that the link to severe infections was not explained by obesity-related chronic conditions, as the association was consistent in people with obesity who did not have metabolic syndrome, diabetes, or heart disease, while the association was also not explained by lifestyle factors such as physical activity.
While the study did not investigate the causes of the association, the researchers say that previous studies have suggested that obesity contributes to a general impairment of immune function, including immune dysregulation, chronic systemic inflammation, and metabolic disturbances.
Professor Kivimaki said: “Our findings suggest that obesity weakens the body’s defences against infections, resulting in more serious diseases. People may not get infected more easily, but recovery from infection is clearly harder.”
The researchers found evidence that losing weight can reduce the risk of severe infections as people with obesity who lost weight had a roughly 20% lower risk of severe infections than those who remained obese.
First author Dr Solja Nyberg (University of Helsinki) commented: “As obesity rates are expected to rise globally, so will the number of deaths and hospitalisations from infectious diseases linked to obesity.
“To reduce the risk of severe infections, as well as other health issues linked with obesity, there is an urgent need for policies that help people stay healthy and support weight loss, such as access to affordable healthy food and opportunities for physical activity. Furthermore, if someone has obesity, it is especially important to keep their recommended vaccinations up to date.”
The authors used infectious disease mortality data from the Global Burden of Diseases (GBD) Study to model the impact of obesity on infectious disease deaths for different countries, regions and globally.
The analysis suggested 0.6 million out of 5.4 million (10.8% or one in 10) infectious diseases deaths globally were linked with obesity in 2023.
The researchers estimated that in the UK, one in six (17%) infection-related deaths can be attributable to obesity, and 26% in the US.
Co-author Dr Sara Ahmadi-Abhari (Imperial College London), who conducted the Global Burden of Diseases (GBD) analyses, said: “Estimates of the global impact give a sense of how large the problem may be, but they should be interpreted with caution. Data on infection-related deaths and obesity in the GBD are not always accurate, particularly in low-resource countries.”
It has long been known that heart attacks occurring in the morning are typically more serious than those that happen at night. While daily variations in stress hormone levels and blood pressure affect cardiac health, these are only part of the picture. There is also the diurnal variation in immune response involved: neutrophils, the body’s ‘first responders’, cause more inflammatory damage in the morning, causing havoc even as they neutralise pathogens.
“They’re the first sentinel, but they come fully loaded,” said Douglas Mann, MD, professor at Washington University School of Medicine in St Louis. “They’re shooting at everything and dumping a lot of toxic granules on the environment. They are indiscriminate in terms of their ability to destroy, and they take out healthy cells in the process.”
But exactly why they are more damaging at night has been a mystery. Now, researchers have found the reason behind this diurnal difference in destructiveness, and also how to tweak the ‘internal clocks’ of these white blood cells so that they cause less damage during sterile inflammation while still protecting against pathogens. Their findings are reported in the Journal of Exploratory Medicine, and are summarised in JAMA news.
Finding the pattern
The researchers, from Spain and Yale University, discovered that the timing of heart attacks significantly affects their severity due to a ‘neutrophil clock’ controlled by circadian rhythms. Neutrophils are more active during the day (activated by the Bmal1 protein) and less active at night (inhibited by the CXCR4 receptor).
Analysing more than 2000 patients with ST-segment elevation myocardial infarction, the researchers found that those who had an MI in the morning suffered worse cardiac damage than those who had them at night. Mouse experiments confirmed this pattern and showed that genetically disabling the Bmal1 protein reduced daytime neutrophil activity, protecting against severe cardiac injury.
This suggests a treatment strategy of tricking neutrophils into remaining in their nighttime inactive state, allowing doctors to reduce inflammation and lessen heart attack damage during daytime hours without compromising the immune system’s ability to fight infections.
Reducing cardiac damage without compromising the immune system
Mice engineered to have high levels of CXCR4 were given a drug compound, ATI2341, which bound to CXCR4 receptors. When heart attacks were induced, the mice showed reduced tissue damage. To test the neutrophils’ pathogen-fighting ability, they were also infected with Staphylococcus aureus or Candida albicans, but the mice were able to overcome the infection – the treated mice even tolerated the Candida infection better than the controls.
Mann explained why controlling the neutrophils was a better option. “Prior trials have tried to neutralise neutrophils or reduce neutrophil numbers entirely,” Mann noted. “But when you get rid of neutrophils, you’re also handcuffing the immune system. Before, it was considered an inevitability that neutrophils killing off infection also meant damaging a lot of tissue.”
The crucial question is of course whether this research in mice can translate to humans.
Luigi Adamo, MD, PhD, director of cardiac immunology at Johns Hopkins University who was not involved in the study, said that the study, one of the first use immune circadian rhythms to modulate inflammation, “offers new insight into neutrophils and a new way to look at this cardiac damage that might even apply to other types of sterile inflammation.”
Adamo struck a note of caution: the extremely low success rate in animal-to-human translation in cardioimmunology. “Immune cells are not always the same when you go from mice to humans,” he said.
Treatment implementation is a major obstacle
Even if this neutrophil clock alteration could be applied to humans, it would be difficult to administer since heart attacks strike without warning.
“If everyone took one of these drugs in the morning when they woke up, maybe it would make heart attacks less severe, but ‘preventive’ means you’re giving it chronically, and I don’t know what would happen with long-term stimulation of that receptor and other cell types,” Mann said. “Their data support the acute application, but in the long term, that’s a whole different story.”
As systemic treatment, the off-target effects of ATI2341 would need to be explored. He also struggled to envision a potential therapeutic solution.
“Today, when you have a heart attack, in most places with hospitals and well-developed health care systems, the patient gets an angioplasty,” Mann said. “The only time this drug could be given would be at the time of reperfusion, when you’re blowing up the balloon and opening up the clot.” Typically, ideal reperfusion timing is within two hours – but neutrophils probably do their damage within a matter of 30 minutes, Mann explained. “It’s a race against time, and I’m curious if [the researchers] can demonstrate that.”
The newly launched, first of its kind, EthiQal Recognition Programme strives to acknowledge professional conduct that reflects a commitment to the delivery of excellent patient care and the reduction of medicolegal risk.
It is aimed at specialist clinicians in private practice and is based on a point system where defined activities qualify for set points that over time convert to premium refunds.
The Programme underpins EthiQal’s pledge to promoting high-quality healthcare, supporting practitioners in building successful, safe practices and managing their medicolegal risk, and aligning individual practitioners’ professional indemnity premiums with their unique insurance risk.
How the Programme works and which activities qualify for point collection are outlined in the Recognition Programme Benefit Guide, with the formal details of the Programme defined in the Terms and Conditions and Benefit Rules documents, which can all be viewed on the EthiQal website: https://ethiqal.co.za/
For more information about EthiQal, click here [https://ethiqal.co.za/contact/] complete the form, and an Advisor will call you back.
