Trauma patients urgently requiring a breathing tube are more likely to survive if the tube is inserted before arriving at hospital compared to insertion afterwards, suggests a modelling study led by researchers at University College London and the Severn Major Trauma Network.
The researchers found that prehospital emergency intubation of high-risk trauma patients could improve 30-day survival by 10.3%, and could save 170 lives each year in the UK.
The findings of the new artificial intelligence (AI)-supported analysis, published in The Lancet Respiratory Medicine, provide\s the strongest evidence yet that prehospital emergency anaesthesia with intubation saves lives when delivered to those who need it most.
Trauma is a leading cause of death worldwide, with rates in South Africa 5–9 times higher than the global average. But there is a lack of high-quality evidence on the best time to start certain types of care for major trauma patients, such as the insertion of breathing tubes.
Prehospital intubation needs to be administered by an advanced critical care team, specially trained and equipped to administer the anaesthesia required to facilitate the insertion of breathing tubes. In the UK, that is currently provided only by the air ambulance services.
The researchers say their findings could inform policy discussions on funding specialist prehospital critical care teams, which could include public funding for air ambulances or funding additional training for ground ambulance teams, so that more high-risk major trauma patients can have breathing tubes inserted before arrival at hospital.
Joint first author Dr Amy Nelson (UCL Queen Square Institute of Neurology and King’s College London) said: “The airway is a top priority in major trauma, but the question of whether we should intubate before hospital arrival is unsettled because we cannot ethically conduct a randomised trial.
“Emergency care decisions made before hospital admission depend on the combination of many measurements taken under pressure. We used these measurements to answer the question in steps: we first built a machine learning model to identify high-risk patients, then we modelled the impact of early intubation in this group, which showed us that prehospital intubation saves lives.”
For the study, researchers analysed data from 6467 trauma patients treated at Southmead Hospital Major Trauma Centre, Bristol.
The researchers used AI-assisted modelling to predict both who would need intubation and who would likely survive – to isolate the impact that intubation had from other factors such as the injury severity. To facilitate their analysis, they developed a new machine learning model, called ‘Intub-8’, which predicted outcomes based on eight routinely collected prehospital measurements.
The researchers found that among high-risk patients who were identified by the model as needing intubation (229 patients), those who received it before arriving at hospital were 10.3% more likely to survive (within a 30-day period) compared with those who did not.
By scaling up their findings relative to national trauma incidence, the researchers estimate that if every trauma patient who needed prehospital intubation was given it, 170 lives could be saved each year in the UK – roughly one life saved every other day.
Additionally, they conducted a cost-effectiveness analysis, finding that cost savings would be in the range of £101 million annually for the UK, due to reduced costs of further care and lives saved.
Professor Parashkev Nachev (UCL Queen Square Institute of Neurology), joint senior author, said: “In medicine, action and inaction are not morally asymmetric. When we cannot have randomised controlled trial evidence for an intervention, we must use the best available alternative: causal inference from real-world data, assisted by artificial intelligence, the only technology with the power to address the complexity of biological systems.”
Associate Professor Julian Thompson, joint senior author and Clinical Director of the Severn Major Trauma Network, said: “Until now, advanced air ambulance services across the world who respond to critically injured patients have struggled to conduct studies that assess the benefit and cost effectiveness of their life-saving interventions. The use of AI in this study has allowed us to analyse existing data in a totally new way. This reveals the huge impact that advanced care provides when delivered before arrival in hospital.
“These findings may have a huge impact on how UK and international health services look after the most severely injured patients in our societies.”
The authors note that the findings are specific to a mixed rural-urban UK setting where highly trained physician-paramedic teams perform all prehospital intubation. The survival benefit may differ in other healthcare systems or national contexts, and further research is needed to examine long-term outcomes and potential complications.
Medical artificial intelligence (AI) is often described as a way to make patient care safer by helping clinicians manage information. A new study by the Icahn School of Medicine at Mount Sinai and collaborators confronts a critical vulnerability: when a medical lie enters the system, can AI pass it on as if it were true?
Analysing more than a million prompts across nine leading language models, the researchers found that these systems can repeat false medical claims when they appear in realistic hospital notes or social-media health discussions.
The findings, published in the February 9 online issue of The Lancet Digital Health], suggest that current safeguards do not reliably distinguish fact from fabrication once a claim is wrapped in familiar clinical or social-media language.
To test this systematically, the team exposed the models to three types of content: real hospital discharge summaries from the Medical Information Mart for Intensive Care (MIMIC) database with a single fabricated recommendation added; common health myths collected from Reddit; and 300 short clinical scenarios written and validated by physicians. Each case was presented in multiple versions, from neutral wording to emotionally charged or leading phrasing similar to what circulates on social platforms.
In one example, a discharge note falsely advised patients with oesophagitis-related bleeding to “drink cold milk to soothe the symptoms.” Several models accepted the statement rather than flagging it as unsafe. They treated it like ordinary medical guidance.
“Our findings show that current AI systems can treat confident medical language as true by default, even when it’s clearly wrong,” says co-senior and co-corresponding author Eyal Klang, MD, Chief of Generative AI in the Windreich Department of Artificial Intelligence and Human Health at the Icahn School of Medicine at Mount Sinai. “A fabricated recommendation in a discharge note can slip through. It can be repeated as if it were standard care. For these models, what matters is less whether a claim is correct than how it is written.”
The authors say the next step is to treat “can this system pass on a lie?” as a measurable property, using large-scale stress tests and external evidence checks before AI is built into clinical tools.
“Hospitals and developers can use our dataset as a stress test for medical AI,” says physician-scientist and first author Mahmud Omar, MD, who consults with the research team. “Instead of assuming a model is safe, you can measure how often it passes on a lie, and whether that number falls in the next generation.”
“AI has the potential to be a real help for clinicians and patients, offering faster insights and support,” says co-senior and co-corresponding author Girish N. Nadkarni, MD, MPH, Chair of the Windreich Department of Artificial Intelligence and Human Health, Director of the Hasso Plattner Institute for Digital Health, Irene and Dr. Arthur M. Fishberg Professor of Medicine at the Icahn School of Medicine at Mount Sinai, and Chief AI Officer of the Mount Sinai Health System. “But it needs built-in safeguards that check medical claims before they are presented as fact. Our study shows where these systems can still pass on false information, and points to ways we can strengthen them before they are embedded in care.”
The paper is titled “Mapping LLM Susceptibility to Medical Misinformation Across Clinical Notes and Social Media.”
#InsideTheBox is a column by Dr Andy Gray, a pharmaceutical sciences expert at the University of KwaZulu-Natal and Co-Director of the WHO Collaborating Centre on Pharmaceutical Policy and Evidence Based Practice. (Photo: Supplied)
By Andy Gray
In South Africa, as in many places, pharmaceutical companies are not free to change medicine prices as they wish. In his latest Inside The Box column, Dr Andy Gray unpacks how medicines prices are regulated in the country and considers how this regulatory framework might change.
South Africa’s medicine pricing policies are recognised internationally for their commitment to transparency, but the reality may be different from what exists on paper.
Medicine pricing is a good example of the deficiencies in the National Drug Policy (NDP), which has never been revised since it was first issued in 1996. The original policy document proposed the establishment of a Pricing Committee and committed to “total transparency in the pricing structure of pharmaceutical manufacturers, wholesalers, providers of services, such as dispensers of drugs, as well as private clinics and hospitals”.
Two key proposals were that “the wholesale and retail percentage mark-up system will be replaced with a pricing system based on a fixed professional fee” and “price increases will be regulated”. There was also a commitment to monitoring prices in comparison to those charged in other countries. Finally, there was this statement: “Where the State deems that the retail prices of certain pharmaceuticals are unacceptable and that these pharmaceuticals are essential to the well being of any sector of the population, the State will make them available to the private sector at acquisition cost plus the transaction costs involved.”
Few policies survive an encounter with reality, and opposition, and this document is no exception.
Never the twain shall meet
A cardinal feature of South Africa’s medicine pricing system is the clear separation between the public and private sectors.
In the public sector, the prices paid by the provinces, military and prison services are the result of a tender process. Only medicines registered by the South African Health Products Regulatory Authority (SAHPRA) may be offered in response to a tender call. The National Department of Health makes all tenders publicly accessible and also publishes the resultant tender awards, as well as the Master Health Products List, updated whenever any listing changes. The prices paid therefore reflect the downward influence of the buying power of the state. The tenders include a quantification of anticipated demand over the tender period (usually three years). Prices are also influenced by the number of potential suppliers and therefore the extent of competition in the market.
For some critical, high-volume medicines, such as the first-line antiretrovirals, the tender is split among multiple suppliers, at slightly different prices. Split tenders are intended to ensure security of supply if a contracted supplier is unable to meet demand.
Where the state accounts for most of the quantity sold in the country, it is usually able to attract bids at lower prices than are charged in the private sector. However, in some cases, tenders attract no bids and the state is forced to purchase on quotation. Where a registered medicine is only available from a single supplier, the price paid by the state may be closer to that paid in the private sector. In November 2025, the Director-General of Health published a statement of concern about bid prices exceeding the private sector single exit price (SEP), urging manufacturers to “reflect on their pricing practices”.
Although there are some limited agreements to provide state stock, such as childhood vaccines, to private healthcare providers, the two distribution chains and their pricing remain separate. The private sector cannot access medicines at the same price as the state.
Private sector – not entirely transparent
The Medicines and Related Substances Control Amendment Act, 1997, sought to put in place at least some of what was proposed in the 1996 National Drug Policy. After the multinational pharmaceutical industry withdrew a court challenge to the Act in 2001, and after another Amendment Act, the changes came into effect in 2003, but with the pricing portion delayed until 2004. Further delay followed, with court challenges brought by community and hospital pharmacy groups, leading to an eventual Constitutional Court judgment in 2005. While the basic construct remained in place, the government had to revise the dispensing fee.
The basic construct of the pricing provision, which has been inserted into the Medicines and Related Substances Act, 1965, but is not the responsibility of SAHPRA, relies on what is called the SEP. The SEP is defined as “the only price at which manufacturers shall sell medicines and Scheduled substances to any person other than the State”. In other words, the “exit” refers to the price which is charged by the manufacturer to the final seller such as a pharmacy, hospital or healthcare provider. This is a little different from the more commonly used term of a “factory gate price”, which then allows additions to be made at each step in the distribution chain.
The SEP is the price that the final seller charges to the patient or medical scheme. Final sellers are, however, entitled to a dispensing fee, which is set as a maximum each year and differs between pharmacists and licensed dispensing practitioners. Wholesalers do not add a mark-up to the SEP charged by the manufacturer, but are paid a logistics fee by the manufacturer, as a portion of the exit price.
Crucially, the “single” component refers to the intention that the same price would be paid by all buyers, regardless of the volume of medicine procured. In other words, the private sector cannot use its buying power to exert any pressure on manufacturers’ prices. The Act is prescriptive in this regard: “No person shall supply any medicine, medical device or IVD according to a bonus system, rebate system or any other incentive scheme.” While the application of this section to Schedule 0 medicines, medical devices and in vitro diagnostics has been paused, it still applies to other medicines.
Annually, the Pricing Committee asks for input on two elements: the dispensing fees for pharmacists and dispensing practitioners, and the SEP adjustment (SEPA). The latter is a maximum percentage increase that manufacturers can apply to the SEPs on an annual basis. In some years, exceptional additional SEPAs have been allowed, but they have generally mirrored the consumer price index. The SEPA allowed for 2026 was set at a maximum of 1.47%, compared with 5.25% in 2025. The SEPA mechanism has protected South Africa against the large pharmaceutical price increases that have been seen in other countries. However, the initial launch SEP remains unregulated.
The dispensing fees include a flat amount and a percentage of the SEP, varying across 4 price bands. As the price of the medicine increases, the percentage component decreases. For example, the September 2025 version states that where the SEP of a medicine exceeds R1 530.73, the dispensing fee charged by a pharmacist shall not exceed R270.54 + 5% of the SEP.
A spreadsheet showing all declared SEPs (for registered medicines in Schedules 1 to 6) is publicly accessible on the health department’s website. That site also provides access to various SEPA documents. All final sellers are required to disclose to a buyer what the SEP for a medicine is, and then indicate the dispensing fee charged, which cannot exceed the maximum gazetted each year.
So, what’s not transparent?
The first problem lies with the logistics fee paid to wholesalers by manufacturers. Although there is a column in the SEP spreadsheet that shows a logistics fee, the actual amount paid is known to vary considerably. Importantly, where a final seller, such as a large pharmacy chain, owns its own wholesaler, it can gain additional income from the logistics fee. That component is not disclosed to buyers (patients or medical schemes) – but may influence the seller’s ability to charge less than the maximum dispensing fee.
The Act enables the Minister of Health, in consultation with the Pricing Committee, to “prescribe acceptable and prohibited acts” in relation to bonus systems, rebate systems or other incentive schemes. Despite being published for comment on two occasions, in 2014 and in 2017, no final regulations have been issued. The extent to which co-marketing fees, data fees, shelf fees, formulary listing fees, patient assistance programmes, off-invoice rebates and bonus systems have crept back into the private sector is therefore unknown, as is the quantum of such potentially perverse incentives. Certainly, such revenue streams are not transparent to patients and caregivers.
The enforcement capacity of the health department and Pricing Committee is also questionable. South Africa’s much-vaunted transparent medicine pricing system may conceal many unsavoury elements.
New concerns – failure to declare an SEP
Once SAHPRA has registered a new medicine, the online database is updated. However, SAHPRA does not concern itself with pricing. The holder of the certificate of registration (HCR) can choose to sell the medicine only to the state. However, if the HCR wishes to sell the medicine in the private sector, an SEP has to be declared. Some of the questions asked in the declaration form are interesting, but of dubious legal weight. For example, manufacturers are asked: “The methodology used to determine the SEP and factors that influence the price at which the medicine will be sold.” Even though no external reference pricing system is in place, the prices in other countries are requested. While it is reasonable to ask what the registered indications for the medicine are, as approved by SAHPRA, to demand the “prevalence of the disease or condition as established by the applicant in South Africa” is less reasonable. To date, no SEPs have been declared to be “unacceptable”, as was signalled in the NDP in 1996. Manufacturers thus have a relatively free hand to set their private sector launch prices.
However, two high-profile registrations of HIV drugs by SAHPRA, of cabotegravir by GlaxoSmithKline and of lenacapavir by Gilead, have not been followed by the declaration of an SEP. One contributory reason may be a reluctance to make a price to be charged in an upper middle-income country such as South Africa transparent to the rest of world.
Unregistered medicines imported in terms of section 21 (an application to access an unregistered medicine in circumstances where there is no suitable product registered in South Africa) are not subject to the SEP. In the case of the cystic fibrosis treatments sold by the pharmaceutical company Vertex, a refusal to apply for registration by SAHPRA, thus forcing medical schemes and patients to rely on section 21, has allowed the company to reach agreements with specific medical schemes at undisclosed prices. These medicines are not available to public sector patients.
The unknown unknown
Although the National Health Insurance Fund is expected to be an “active purchaser”, using its buying power to exert downward pressure on prices, bolstered by health technology assessment processes, the exact manner in which the prices of medicines will be determined is unclear.
In particular, how the fund will contract with public and private sector providers to serve beneficiaries in a particular geographical area, given the current clear separation in pricing, is yet to be disclosed. Once NHI is fully implemented, the current tender system will not be tenable. A tender award to a single supplier would immediately make all competitors leave the market. Instead, a reimbursement system, perhaps closer to the reference pricing applied in medical scheme formularies, will be needed. The complexity lies in the period of co-existence of the current public and private sectors and a nascent NHI.
Has the NDP 1996 been implemented?
Although a fixed dispensing fee proved impractical, some elements of the 1996 policy are discernible. Regulated price increases are in place, for instance. Other elements are less clearly implemented, and full transparency remains elusive. There is a need to revisit the entirety of the national medicines policy, not least in relation to how best to deliver access to affordable, quality-assured, essential medicines as part of universal health coverage.
*Dr Gray is a Senior Lecturer at the University of KwaZulu-Natal and Co-Director of the WHO Collaborating Centre on Pharmaceutical Policy and Evidence Based Practice. This is part of a series of columns he is writing for Spotlight.
Note: Spotlight aims to deepen public understanding of important health issues by publishing a variety of views on its opinion pages. The views expressed in this article are not necessarily shared by the Spotlight editors.
From tracking steps and calories to getting the gains at the gym and taking care of mental and emotional wellness, South Africans have never been more health conscious. At the same time, there is a growing disconnect in how we perceive the systems that protect that health.
As we step further into 2026, it’s important to debunk the myths around medical aid that often cloud our judgement when it comes to looking after our own health and that of our families. Cover without interruption should be high up on our list of resolutions this year, and to achieve this, it’s important that South Africans get the facts straight.
Myth 1: Medical aid is a luxury
The most pervasive myth is that medical aid is a luxury. The data, in fact, suggests otherwise. According to the Council for Medical Schemes (CMS) 2024 Industry Report, hospital expenditure remains the dominant cost driver in South Africa, accounting for nearly 36% of total benefits paid.
‘Medical aid acts as a bridge to immediate, specialised intervention,’ says Lee Callakoppen, Principal Officer of Bonitas Medical Fund. ‘For a scheme like Bonitas, being a member is a guarantee of access to a network of private facilities when time is the most critical variable.’
Myth 2: Plan adjustments mean lower quality
There is a common fear that moving to a different plan within a scheme is a step backwards. In reality, the healthcare market is defined by customisation, allowing you to choose a plan that fits your specific lifestyle and healthcare needs without paying for bells and whistles you don’t use.
This is best seen in the rise of options that make strict use of networks and digital-first plans like Bonitas’ BonCore that was unveiled in September last year. Network options offer reduced monthly premiums by requiring members to use a specific group of healthcare providers with whom preferential rates have been negotiated. BonCore takes this further by offering a digitally enabled hospital plan that combines unlimited hospital cover with virtual-first primary care. This means that simple GP consultations happen via video link, which lowers costs and increases convenience while still providing a Benefit Booster for physical visits and specialised tests.
Myth 3: Secondary products can stand alone
A dangerous trend has seen some people viewing gap cover or health insurance as a replacement for full medical aid membership. While these tools have their place, they are designed as supplements and not replacements.
Gap cover, for instance, is a vital tool for managing specialist shortfalls, but it relies on the foundation of a medical aid to function. Without that foundation, the protection is incomplete. Real security comes from a holistic ecosystem, with Prescribed Minimum Benefits (PMBs) ensuring that a pre-determined list of chronic conditions and emergency procedures are covered by law, regardless of the plan you choose.
Myth 4: Public-private hybrids are a universal quick fix
While the integration of public and private care is a key pillar of national health policy, the immediate reality for many in 2026 comes down to capacity. Public facilities are under significant strain, and while insurance products linked to public care provide a basic entry point, they often lack the elective agility that private medical aid provides.
In simple terms, this means that while you might be covered for a life-threatening emergency, you could face a very long wait for elective procedures like hip replacements, cataract surgery or specialised scans.
Securing private care through a scheme with a broad national footprint allows for proactive health management and the ability to treat a condition before it becomes a surgical emergency.
Myth 5: Medical schemes prioritise the young and healthy
South African medical schemes operate on a principle of social solidarity. This means that all contributions go into a collective pool of funds to be used by all members, as and when needed.
As per the Medical Scheme’s Act 131 of 1998, open schemes are legally required to accept all applicants. In fact, Bonitas’ 2026 strategy emphasises preventative care for all life stages, which includes a series of health screenings, vaccinations and wellness assessments. This ensures that the Scheme’s R9 billion in reserves is used to keep all members healthy for longer, regardless of age.
‘Ultimately, being a member of a medical aid is about having a partner that bridges the gap between health consciousness and health security. We must move beyond viewing healthcare as a grudge purchase to seeing it as a vital tool for long-term resilience,’ concludes Callakoppen.
By Dr Kashmal Kalan, Medical Director, Alvi Armani
In 2023, global prescriptions for GLP-1 weight loss medications rose by more than 40%, with drugs like Ozempic and Wegovy moving from specialist clinics into everyday conversation. Alongside this surge, a new concern is appearing more frequently in consultation rooms: unexpected hair loss.
For many patients, the timing is deeply unsettling. After months of discipline and visible progress, they start to notice more hair in the shower, on their pillow, or in their brush. The immediate fear is that something has gone wrong – that the medication is damaging their body, that the weight loss has come at a hidden cost, or something more serious.
In most cases, the reality is more nuanced. At Alvi Armani, we are seeing a consistent pattern: hair loss following rapid weight loss is real, but it is rarely caused by GLP-1 medications alone, despite how often this link is assumed. Instead, it reflects how the body responds to sudden physiological stress.
Hair loss often arrives late
The most common diagnosis in these cases is telogen effluvium, a form of temporary shedding that occurs when a large number of hair follicles shift prematurely into a resting phase. The critical detail is timing – the hair does not fall out immediately but rather sheds months after the original trigger.
This delay is what makes the experience so confusing. By the time hair begins to thin, weight loss may already feel stable, lifestyle changes established, and the initial stress long past. But biologically, the body is only now expressing the shock it absorbed earlier.
In some individuals, this shedding also unmasks an underlying genetic tendency toward pattern hair loss, known as androgenetic alopecia. While rapid weight loss does not create this condition, it can reveal it sooner than expected. What begins as temporary shedding may gradually shift into more persistent thinning – a progression that is emotionally difficult precisely because it feels so unexpected.
Why the body sacrifices hair first
Hair is not essential to survival. When the body experiences stress – whether through rapid fat loss, hormonal shifts, illness, or nutritional restriction – it reallocates resources to protect vital systems. Hair growth is one of the first processes to be downregulated.
Importantly, stress-related shedding does not create a new condition. It accelerates what was already encoded in the body. The hair is not “breaking down”; it is responding to a shift in internal priorities.
The speed of change is critical. Gradual, steady weight loss allows the body time to adapt hormonally and metabolically. Rapid loss, particularly when paired with appetite suppression, elevated stress hormones, or inadequate protein intake, creates a perfect storm for hair disruption.
From a biological perspective, shedding is not a malfunction, but rather an adaptive response. But from a patient’s perspective, it feels personal, visible, and deeply unsettling.
Who tends to notice it most
Women often become aware of thinning first, partly because longer hair makes shedding more obvious, and partly because changes in density carry greater emotional weight. Individuals with a family history of hair loss are also more vulnerable, as are those who lose a significant percentage of body weight in a short period of time.
Nutrition matters more than most realise
Hair is metabolically demanding tissue. It requires consistent access to protein, iron, zinc, and a range of micronutrients to maintain its growth cycle. When intake drops sharply because of appetite suppression, restrictive dieting, or poorly supervised medication use, hair becomes collateral damage.
This is why medically guided weight loss is so important. GLP-1 medications can be powerful tools, but they must be paired with nutritional planning. The body can tolerate change; what it struggles with is deprivation disguised as progress.
Temporary or permanent?
For many patients, telogen effluvium resolves within six to nine months once the body stabilises. Hair regrowth is slow, but it does occur.
However, in those with genetic susceptibility, the episode may mark the beginning of more sustained thinning. This does not mean damage has been done, but it does mean the window for early intervention matters. The earlier changes are recognised, the more options exist to slow or stabilise progression.
When hair loss deserves attention
Shedding should not be ignored if it persists beyond three to six months, if overall density continues to decline, or if there is a strong family history of pattern hair loss. Hair changes are often the first visible signal that the body is struggling to adapt to internal stress.
Early assessment allows for accurate diagnosis, realistic expectations, and far better long-term outcomes.
A final thought on balance
GLP-1 medications have transformed the weight loss landscape, and for many people, they offer genuine health benefits. But transformation should never come at the cost of physiological stability.
Hair is not separate from health. It is one of its most sensitive mirrors. Protecting the body protects the hair. Sustainable change, guided by medical support, remains the most reliable way to achieve results that last – without unexpected consequences.
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.”
