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Novel Research Reveals the Active Role that Skin Cells Play in Rabies Infection

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New findings identify keratinocytes as replication hubs and immune responders, contributing to the risk of rabies infection from superficial scratches or minor bites

Skin cell (keratinocyte)
This normal human skin cell was treated with a growth factor that triggered the formation of specialised protein structures that enable the cell to move. We depend on cell movement for such basic functions as wound healing and launching an immune response. Credit: Torsten Wittmann, University of California, San Francisco

While it was previously thought that keratinocytes (skin cells) were only passive conductors that allow the rabies virus to pass through, novel research reveals that these cells play a much more active role. The findings of a new study in the Journal of Investigative Dermatology (JID), published by Elsevier, provide direct evidence that keratinocytes can support viral replication and transmit the rabies virus to neurons. The investigators offer a mechanistic explanation for how superficial skin exposures from scratches or minor bites by dogs and bats can lead to neuroinvasion, contributing to the risk of infection.

Rabies is a fatal zoonotic infection caused by rabies virus (RABV), responsible for at least 59 000 human deaths per year. The virus is transmitted through the saliva of infected animals. While most cases are caused by dog bites, superficial exposures such as bat bites or scratches can also lead to infection, although the underlying mechanisms remain poorly understood.

“In our previous work, we discovered that keratinocytes – cells that form the epidermis, the outermost layer of the skin – were infected at the site of entry of the rabies virus, both in natural and experimental infections. This was unexpected, as rabies pathogenesis has traditionally focused on muscle cells and motor neurons,” explains lead investigator Corine H. Geurts van Kessel, MD, PhD, Department of Viroscience, Erasmus Medical Centre, Rotterdam, The Netherlands. “Given the strategic position of keratinocytes at the skin barrier and their close proximity to sensory nerve endings, we wanted to understand whether these cells are simply bystanders or active participants in early rabies infection and neuroinvasion.”

The investigators used primary human keratinocyte cultures to investigate susceptibility to rabies virus infection and characterise the resulting antiviral immune responses. Three viral strains were tested: a vaccine strain and two wild-type (“street”) strains derived from fatal human cases associated with bat and dog exposures. The dog-associated strain caused only minimal infection and limited keratinocyte immune activation, whereas the other two strains infected keratinocytes more readily and triggered a pronounced antiviral response.

To simulate the close contact between keratinocytes and intra-epidermal nerve endings, a co-culture model of keratinocytes and neurons was developed. In this model, virus produced in infected keratinocytes was successfully transmitted to adjacent neurons, giving the virus a direct route into the nervous system. Once the virus has established infection in the central nervous system, it is almost inevitably fatal.

“Our study demonstrates that the skin might play a more important role in rabies infection than previously recognised. We were particularly surprised by the strong antiviral response mounted by keratinocytes to the bat-related rabies virus strain,“ notes co-investigator Keshia Kroh, PhD candidate, Department of Viroscience, Erasmus Medical Centre, Rotterdam, The Netherlands. “Wild-type rabies viruses are known for their immunosuppressive capacities, and we expected an immune evasive effect in keratinocytes. Instead, we observed the opposite. This raises new questions about how keratinocyte-derived immune responses influence overall disease progression in rabies and other viral infections of the skin.”

This in vitro co-culture model is the first to study rabies virus entry to the nervous system across a cell barrier. Future in-depth studies should be performed to provide mechanistic insight into the differential strain tropism, the interactions of infected keratinocytes with immune cells, and the mechanisms of neuroinvasion from superficial skin contact.

According to the World Health Organization (WHO), any transdermal exposure (including small scratches or abrasions) should be assessed as a potential rabies risk and managed appropriately based on exposure category and clinical context.

“Our study provides a biological rationale for these recommendations,” says co-investigator Carmen W.E. Embregts, PhD, Department of Viroscience, Erasmus Medical Centre, Rotterdam, The Netherlands. “At the same time, it is important to emphasise that the risk of rabies virus infection via superficial exposures depends on multiple factors, including the nature of the exposure and the epidemiological setting. Rather than causing alarm, our findings support informed decision-making. Awareness that superficial skin exposures can represent a route of neuroinvasion helps ensure that potential risks are recognised and evaluated appropriately, while treatment decisions remain guided by established public health criteria.”

“The data in this study support the increasingly recognised concept that cells in the skin are in snug communication with the nervous system. That a scratch or bite is needed for the transmission of rabies is further evidence of the importance of an intact skin barrier in health,” observes JID Associate Editor Ethan Lerner, MD, PhD, Associate Professor of Dermatology, Harvard Medical School, and Massachusetts General Hospital, Boston, MA, USA.

Source: Elsevier

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AI Model Predicts How CPAP Affects Cardiovascular Risk in Obstructive Sleep Apnoea

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Photo by Navy Medicine on Unsplash

Mount Sinai researchers have created an analytic tool using machine learning that can predict cardiovascular disease risk in millions of patients with obstructive sleep apnoea, according to findings recently published in Nature Communications Medicine.  

The team said their study is the first to provide estimates of whether continuous positive airway pressure (CPAP), a widely used therapy for obstructive sleep apnoea, will increase or decrease an individual’s cardiovascular risk. It highlights the potential for precision medicine and varied approaches to tailor clinical care and reduce cardiovascular disease risk in vulnerable patients. 

Obstructive sleep apnoea is a common, serious condition in which breathing repeatedly stops and starts during sleep. It is associated with elevated risks for cardiovascular disease, including stroke and heart disease. CPAP, which provides a continuous stream of pressurised air through a mask and helps eliminate breathing disturbances during sleep, remains the most effective treatment for sleep apnoea. However, prior large studies have not shown that CPAP lowers risks for cardiovascular disease in patients with this disease.  

The Mount Sinai researchers used a machine learning algorithm to create an analysis model that predicts how CPAP could affect an individual’s cardiovascular health – estimating each patient’s likeliness of benefit or harm from the therapy, based on their sleep and health information.  

“Our findings represent a significant advancement in personalised medicine, moving away from a one-size-fits-all strategy in the treatment of obstructive sleep apnoea,” said co-corresponding author Neomi A. Shah, MD, MPH, MSc, ATSF, Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine) and Artificial Intelligence and Human Health, and System Vice Chair of Faculty Affairs for the Department of Medicine at Icahn School of Medicine at Mount Sinai. “This underscores the value of new data-driven approaches like our model to assist clinicians in making informed decisions about CPAP treatment recommendations, enhancing personalised care to meet the individual needs of every patient.” 

The Mount Sinai team analysed data from the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, the largest clinical cohort evaluating CPAP for cardiovascular disease prevention with more than 2,600 participants from 89 sites in seven countries, to estimate individualised treatment effect scores. They considered more than 100 predictors from sleep and health information to establish 23 key baseline features, such as prior medical conditions and smoking status, in their analysis model.  

The researchers found that treatment response significantly varied across the cohort. The model identified a subgroup who were expected to have improved cardiovascular risk with CPAP treatment; participants in this subgroup who were randomly assigned to receive the therapy experienced a 100-fold improvement in future cardiac risk compared with patients from this subgroup on usual care. Conversely, those in a subgroup predicted to be harmed by the therapy experienced a greater than 100-fold increase in cardiovascular disease outcomes, including recurrent strokes and heart attacks, when receiving CPAP compared with usual care.  

“These results demonstrate the power of machine learning for prediction of treatment effects in an era of precision medicine; however, such models require careful validation to prove their utility in clinical practice,” said co-primary author Oren Cohen, MD, Assistant Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine) at the Icahn School of Medicine. 

“Artificial intelligence in medicine must move beyond pattern recognition to causal reasoning,” said co-corresponding author Mayte Suarez-Farinas, PhD, Co-Director for the Division of Biostatistics and Data Science, and Professor of Population Health Science and Policy, and Artificial Intelligence and Human Health, at the Icahn School of Medicine. “By estimating individualised treatment effects over time using randomised clinical trial data, we move predictive AI toward decision-support tools grounded in causality and capable of informing real-world treatment decisions and improving outcomes.”  

Source: Mount Sinai

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Early Warning Signs of Brain Infection in Children Identified in New Study

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Photo by Chayene Rafaela on Unsplash

Despite new diagnostic methods and expanded vaccination programmes, many children in Uganda continue to suffer from severe brain infections. This is shown in a new study from Karolinska Institutet, published in The Lancet Regional Health – Africa. The researchers’ analysis highlights simple clinical signs that can help healthcare providers more quickly identify children at high risk of death.

The study followed 212 children aged 0 to 12 who were treated for suspected central nervous system infections at two hospitals in southwestern Uganda. Fifteen per cent of the children died during hospitalisation, and 18 per cent were discharged with neurological disabilities such as seizures or muscle weakness. Malaria and the bacterium Streptococcus pneumoniae were the most commonly identified causes.

Simple observations can provide crucial information

“Our results show that even in settings where advanced diagnostics are not always available, simple clinical observations can provide crucial information about which children are in greatest need of rapid care,” says Phuthumani Mlotshwa, doctoral student at the Department of Global Public Health and the study’s first author.

The infections were caused by several different microorganisms. Malaria was detected in 20 per cent of the children, and bacteria in the cerebrospinal fluid in 11 per cent. For nearly half of the cases, no specific pathogen could be identified, which the researchers say underscores the need for improved diagnostic tools.

“The combination of high mortality and significant disabilities among survivors shows that we need to strengthen prevention, diagnostics, and follow-up,” says Giulia Gaudenzi, researcher at the same department and the study’s senior author.

Source: Karolinska Institutet

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Increasing Fruit, Fibre, Dairy and Caffeine Linked to Lower Risk of Tinnitus

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But quality of evidence low and further studies needed to verify the relationship, say researchers

Photo by Dylann Hendricks on Unsplash

Increased consumption of fruit, dietary fibre, dairy products and caffeine may be associated with a reduced risk of tinnitus (ringing in the ears), suggests an analysis of the available evidence, published in the open access journal BMJ Open.

The researchers stress that their findings can’t establish a direct (causal) relationship and should be interpreted with care because of the low quality of the evidence. But they say possible reasons may involve the protective effects of these diets on blood vessels and nerves, as well as their anti-inflammatory and antioxidant properties.

Tinnitus is the perception of sound (ringing, buzzing or clicking) when there’s no external source. Data suggests it affects around 14% of adults worldwide and is associated with depression, anxiety, stress, and in severe cases, suicide.

There is no cure, but treatments such as counselling, behavioral therapy, medications, and hearing aids can help to reduce symptoms.

Diet can also have a significant impact on tinnitus. It’s thought that eating high-quality nutrients can have a positive effect on hearing by improving blood flow to the inner ear and reducing oxidative damage and inflammation. But previous studies show conflicting results and it’s still uncertain which specific foods worsen or relieve symptoms.

To explore this further, the researchers trawled research databases looking for studies linking tinnitus and diet in adults published up to May 2024.

They found eight observational studies involving 301,533 people that assessed 15 dietary factors using validated questionnaires that were of suitable quality to include in their analysis.

The dietary factors included carbohydrates, caffeine, eggs, fruits, fibres, fat, meat, protein, sugar, fish, vegetables and dairy.

The combined findings revealed that increased consumption of fruit, dietary fibre, dairy products and caffeine was associated with a reduced occurrence of tinnitus. These reductions were 35% for fruit intake, 9% for dietary fibre, 17% for dairy products, and 10% for caffeine intake.

No associations were found between other dietary factors and tinnitus and results were consistent after further analyses, although the authors note that the association between caffeine intake and tinnitus remains contentious.

The authors acknowledge that due to the observational design of included studies, causality cannot be established, and the relatively small number of included studies may have led to certain conventionally accepted beneficial dietary factors (such as vegetables and eggs) not demonstrating significant differences.

However, they suggest that “the primary underlying mechanisms may involve the protective effects of these diets on blood vessels and nerves, as well as their anti-inflammatory and antioxidant properties” and say further large-scale studies are needed “to complement and verify the relationship between dietary intake and tinnitus.”

Source: BMJ Group

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From Gogo to Citizen Scientist – The Women Helping to Defeat Malaria

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World Malaria Day is commemorated every year on 25 April to raise awareness and highlight the global efforts against malaria.

Photo by Ayo Ogunseinde on Unsplash

by Dr Taneshka Kruger, Project Manager: University of Pretoria Institute for Sustainable Malaria Control (UP ISMC) and Prof Tiaan de Jager, Director: UP ISMC

Eliminating malaria requires effort that goes far beyond our laboratories. It also happens in homes, villages and clinics, where gogos (grandmothers), mothers, young women and other citizen scientists play a vital role in prevention, early action and creating public awareness.

On 25 April, we commemorate World Malaria Day. This day is aimed at raising awareness about one of the world’s oldest and deadliest diseases, while also recognising the progress we’ve made in controlling and eliminating it. This year’s theme, ‘Driven to end malaria: Now we can. Now we must.”, is a reminder that success depends not only on medicine and science, but also on the people who protect families and strengthen communities every day.

Malaria remains a life-threatening disease transmitted by female Anopheles mosquitoes infected with the Plasmodium parasite. Globally, hundreds of millions of cases are reported each year, with the overwhelming burden falling on sub-Saharan Africa. The most vulnerable groups include pregnant women, children under five and older persons.

Why women and children face greater malaria risks

Pregnancy reduces a woman’s immunity to malaria, increasing the risk of infection and severe illness. Malaria during pregnancy can lead to maternal anaemia and serious complications such as miscarriage, premature birth, stillbirth and low birth weight. Low birth weight is one of the leading contributors to neonatal mortality and can affect a child’s long-term development.

Children under five continue to carry the heaviest malaria burden. In Africa, they account for roughly three-quarters of malaria-related deaths. Their immune systems are still developing, making prevention, early diagnosis and prompt treatment essential for survival.

The family members who spot danger first

In many rural communities, mothers – and especially grandmothers – are the backbone of family life. They shape household health practices, encourage clinic visits, and ensure children use preventative measures against malaria, such as sleeping under protective nets, where possible. Their lived experience gives them influence and trust, and when equipped with up-to-date malaria information they become powerful advocates for prevention. They are often the first to notice symptoms such as fever, fatigue or vomiting, and frequently help decide when and how medical care is sought.

Women also care for elderly family members, who may have weaker immune systems and be more vulnerable to complications from malaria. In areas where clinics are far away or transport is limited, their vigilance can be lifesaving.

Young women – whether students, entrepreneurs, community workers or volunteers – also play an increasingly important role in sharing reliable malaria information. They help bridge the gap between scientific knowledge and everyday community life, promoting practical actions such as:

  • Seeking early testing when symptoms such as fever appear
  • Reducing mosquito breeding sites through environmental management
  • Using preventative strategies to avoid mosquito bites
  • Consistent use of insecticide-treated bed nets where available
  • Attending antenatal clinics for intermittent preventive treatment in pregnancy (IPTp), in countries where these programmes are offered.


Through each of these actions and more, women’s leadership strengthens community resilience and promotes healthier futures.

Young women spreading life-saving knowledge

One of the most encouraging developments in rural malaria response is the rise of women citizen scientists. Through training programmes supported by research institutions, women from local communities are gaining skills to assist with field data collection and malaria surveillance.

In malaria research conducted by the University of Pretoria Institute for Sustainable Malaria Control in Limpopo’s Vhembe District,  women citizen scientists have contributed by:

  • Engaging tribal authorities and communities about the purpose of the research and how communities can benefit
  • Collecting health data to assess the impact of malaria control methods on people and the environment
  • Collecting mosquito samples for vector surveillance and climate-related research
  • Gathering knowledge, attitude and practice data through surveys
  • Conducting interviews before and after interventions to assess effectiveness
  • Running focus groups to better understand community needs, behaviours and challenges.

By participating in field research, these women gain scientific skills while contributing directly to malaria control strategies. Their involvement helps ensure that research is done in local languages, reflects lived realities and leads to practical action communities can trust and use.

Just as importantly, this model expands women’s roles beyond traditional caregiving expectations. It positions them as knowledge holders, data contributors and active partners in scientific discovery. It also shows young girls in these communities that science is accessible, relevant and open to them.

From community member to citizen scientist

When mothers, gogos and young women understand the risks malaria poses – especially to pregnant women and children under five – they are better equipped to protect their families. When they are empowered as citizen scientists, they move from being passive recipients of health messaging to active drivers of change, contributing to local malaria elimination efforts. Their combined role as caregivers, educators and research partners strengthens both households and health systems.

On this World Malaria Day, we should recognise and honour the women who care for feverish children through the night, accompany pregnant daughters to clinics, share trusted advice with neighbours, and step into fields and villages as trained citizen scientists. By investing in women’s knowledge, leadership and participation at home, in communities and in science, we move closer to a future free from this preventable disease.

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How Far Will 800 New Posts Take Western Cape Health?

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More than 33 000 healthcare workers helped patients more than 20 million times in the Western Cape in the last financial year. (Photo: QuickNews)
21st April 2026

By Christina Pitt

The Western Cape health department is ramping up its workforce with 800 new frontline posts. After years of austerity and with long lists of vacancies, questions now turn to how soon the new posts will translate into staff on the ground.

The Western Cape health department is adding more than 800 staff to frontline and support services in a bid to strengthen a health system in which hiring has been stifled by years of austerity.

Health MEC Mireille Wenger announced a recruitment drive, which includes 316 nurses, 124 doctors and 80 emergency medical personnel. For medical workers to have more time at their patients’ bedsides, she said this plan also targets 38 allied health professionals, such as physiotherapists and dieticians, alongside 278 administrative and management staff.

As it stands, more than 33 000 staff in the province helped patients more than 20 million times in the last year, according to Wenger. For public hospitals and clinics, the news of the new jobs offers some hope that the constant pressure on staff capacity will be relieved.

One example of where the new jobs may make a difference is with surgical backlogs in the province. Of the nearly 100 000 people waiting for surgery in 2025, 87 975 have been waiting for more than a year, while 20 027 have been on the list for more than 60 months. Some of these people entered the system during the height of the Covid-19 pandemic and have been left in limbo through years of budget cycles and hiring freezes.

The budget paradox

While governance has been poor in most of South Africa’s nine provincial health departments, with corruption and looting in Gauteng being a particular concern, the Western Cape health department has received seven consecutive clean audits, maintained stable leadership and largely avoided controversy.

As part of a total R106.8 billion package over three years, the Western Cape health department’s 2026/27 budget is R34.47 billion, which is a 6.25% increase from last year.

When adjusted for inflation, provincial health budgets have been falling for most of the last decade. This has contributed to constrained hiring budgets and exacerbated staff shortages. The tide finally turned with above-inflation increases in the 2025 and 2026 budgets – although belts remain very tight.

Professor Alex van den Heever, Chair of Social Security Systems Administration and Management Studies at the University of the Witwatersrand, said that the Western Cape’s health department is a relatively well-run machine yet is dogged by underfunding.

Understanding this requires a look at how provincial health departments are funded.

While provincial health departments get some funds via sources such as provincial revenue and conditional grants, most of their funding flows from the province’s slice of the national budget. For the 2026/27 financial year, the country’s nine provinces was allocated R810.5 billion.

How much each province gets is determined by the provincial equitable share formula, which has been under review since 2015. The provincial equitable share formula considers factors, such as the size of the school-aged population and the number of people living in poverty. Its health component considers factors like the population without medical aid, adjusted for health risk, medical aid membership, and clinic and hospital visits.

Provinces decide how they divide their share of the budget between their provincial departments.

There are however some issues with the provincial equitable share formula. Firstly, it makes use of certain data from the South African census, which means that the information does not reflect current demographic and service realities, said Van den Heever (the census is conducted only every 10 years). Secondly, the usefulness of the results from the latest census of 2022 is in question because certain data sets, such as income, mortality, fertility, and employment figures, were missing.

As a result, National Treasury has been unable to fully update its calculations to factor in the census 2022 data, contributing to a lag in how population changes are reflected in budget formulas. As far as we can tell, National Treasury has relied on datasets updated at different times in the year, such as Stats SA’s mid-year population estimates, allowing it to phase in changes gradually rather than introduce sudden adjustments.

Broadly, Van den Heever said the result is a system forced to pick up the tab for a population the national budget hasn’t yet acknowledged. Citing an example linked to health, he says the formula ignores patients who travel from other provinces to access specialist care at tertiary hubs like Groote Schuur Hospital in Cape Town.

The claw-back

Some of the vacancies in the Western Cape health department reflect periods when the government cut funding due to broader economic challenges, Doctor Saadiq Kariem, the department’s Chief Operating Officer, told Spotlight.

Indeed, between 2021 and 2024, the province absorbed an R8.4 billion reduction in its budget allocation.

This has forced leadership to make some tough calls, including vacancies for frontline services like health. Kariem explained: “It was a process of consciously delaying the filling of those posts so that we could make up for the loss in funding. Sometimes we, along with local managers, decided to shift posts from a vacancy to another part of the service platform based on service needs and pressures.”

“You know, these are heart wrenching choices because all of those posts are absolutely essential and I know that not filling them will have an impact on the service provision and result in poorer health outcomes. So yes, the austerity measures had a significant impact on the post filling rate,” he added.

According to the health department’s annual report, 3 737 people left the department’s employment in the 2024/2025 financial year. By the end of March 2025, 2 772 funded posts remained vacant.

Nationally, vacancies among nursing staff are particularly acute. As of 2023, across enrolled, auxiliary, community service, professional, primary healthcare and specialist nurses, there were about 14 000 vacant posts across the country.

Sabelo Ntshanga, Western Cape provincial secretary of the Democratic Nursing Organisation of South Africa, said burnout caused by workload is the main driver of attrition.

“The reality is that it’s not being filled quickly. It takes up to a year sometimes while the demand in the communities remains high,” he said. “Burnout is underreported and when the nurses get sick from burnout, that’s another burden on top of the shortage of staff.”

Overall, while the 800 new posts represent a step in the right direction, it appears to be more about holding the line than an actual growth spurt. As Kariem says, it represents an effort to “claw back” towards a stable staffing baseline while attempting to invest in future service capacity.

The red tape

Things won’t change overnight though. Wenger noted in her speech that “it will take time to fill these posts”.

Kariem explained that recruitment follows a multi-stage process as vacancies are advertised, followed by shortlisting and interviews. Final appointments then require approval at different levels of the system, depending on the seniority and specialty of the role. “We see delays throughout the process,” he said. “Once there is the ability to advertise a post, we have to give sufficient time for an advert to run… then for interviews and for permissions to follow.”

This means that even funded posts can remain unfilled for extended periods as they move through administrative and approval processes.

Adding further delays to an already complex process, the National Treasury and the Department of Public Service and Administration (DPSA) advised cost-containment measures in October 2023, which was extended until March 2025. It required additional approvals before recruitment could proceed.

Wenger bemoaned these regulations when it was rolled out. “The DPSA’s recent regulations, intended to slow down recruitment, are doing real harm to large service delivery departments like Health. Staff retire or move on, and yet our system lacks the agility to replace them fast enough. This leaves remaining healthcare workers overburdened, and services strained,” she said.

At the same time, not all vacancies can be filled due to shortages of suitably qualified candidates, particularly specialist nurses. Kariem explained that this in part reflects longer-term gaps in investment in postgraduate training. He said the department is using recent budget increases to strengthen human resources information systems to better identify skills gaps and fill vacancies.

These staffing pressures also affect training and retention. Ntshanga said they limit the system’s ability to release nurses for professional development, constraining career progression and contributing to low morale.

At Groote Schuur Hospital, the department noted that nursing staff shortages have affected multiple units across the hospital in 2024/25, contributing to reduced service capacity.

For Ntshanga, the new posts are a small drop in a very large bucket. “As much as it is a good deed from the department, it doesn’t come close to what we need on the shop floor,” he said.

Republished from Spotlight under a Creative Commons licence.

Read the original article.

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New Report Highlights Fructose as a Key Driver of Metabolic Disease

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Researchers emphasise fructose’s unique role in obesity, metabolic syndrome and other chronic diseases

Photo by Kobby Mendez on Unsplash

A new report, published in Nature Metabolism, is shedding light on the distinct and underappreciated role of fructose in driving disease, separate from its role as a simple source of calories.

Researchers examine how common dietary sweeteners, including table sugar (sucrose) and high-fructose corn syrup, impact human health. While both contain glucose and fructose, fructose has unique metabolic effects that may more directly contribute to obesity and related conditions.

“Fructose is not just another calorie,” said Richard Johnson, MD, professor at the University of Colorado Anschutz and study lead author. “It acts as a metabolic signal that promotes fat production and storage in ways that differ fundamentally from glucose.”

The report outlines how fructose metabolism bypasses key regulatory steps in the body’s energy-processing pathways. This can lead to increased fat synthesis, depletion of cellular energy (ATP) and the production of compounds linked to metabolic dysfunction. Over time, these effects may contribute to metabolic syndrome, a cluster of conditions that includes obesity, insulin resistance and cardiovascular risk.

Importantly, the authors emphasise that fructose’s impact extends beyond dietary intake alone. The body can also produce fructose internally from glucose, suggesting that its role in disease may be broader than previously recognised.

The findings come amid ongoing concern about rising rates of obesity and diabetes worldwide. Although some countries have seen declines in sugary beverage consumption, overall intake of “free sugars” remains above recommended levels in many regions and continues to increase in others.

While fructose may have once served an evolutionary purpose, helping the body store energy that can aid survival during times of food scarcity, the researchers argue that in today’s environment of constant food availability, these same mechanisms now contribute to chronic disease.

“This review highlights fructose as a central player in metabolic health,” said Johnson. “Understanding its unique biological effects is critical for developing more effective strategies to prevent and treat metabolic disease.”

By Kelsea Pieters

Source: Colorado University Anschutz

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Triple-negative Breast Cancer Survival Nearly Doubled with New Treatment

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Results of a global, multicentre, phase III clinical trial indicate that datopotamab deruxtecan (Dato-DXd) is effective in improving survival for untreated, advanced triple negative breast cancer (TNBC) 

Photo by National Cancer Institute on Unsplash

A global, multicentre phase III trial, TROPION-Breast02, led by a senior medical oncologist and researcher from the National Cancer Centre Singapore, has demonstrated a significant breakthrough in improving the survival of patients with untreated, advanced triple negative breast cancer (TNBC) using the novel antibody-drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd). Published in the Annals of Oncology, the findings demonstrate the potential of Dato-DXd as an effective new treatment option for this aggressive disease.

“In the TROPION-Breast02 trial, first-line Dato-DXd demonstrated clinically meaningful and significant improvements in progression-free survival and overall survival for these TNBC patients, and a higher overall response rate compared with chemotherapy. As a medical oncologist treating triple-negative breast cancer patients for the past 20 years, I am deeply encouraged that this data shows we now have a much-needed new tool to help women affected by this devastating disease,” said lead investigator Prof Rebecca Dent, Deputy CEO (Clinical) and Senior Consultant in the Division of Medical Oncology at the National Cancer Centre Singapore.

The burden of triple negative breast cancer (TNBC)

Breast cancer is the leading cause of cancer death in women globally. Approximately 10 to 20% of breast cancers are TNBC, an aggressive subtype that disproportionately affects young women under the age of 40. TNBC is associated with early recurrence, high likelihood of metastasis and shorter survival. In recent years, TNBC patients with PD-L1-positive tumours or germline BRCA mutations have been eligible for immunotherapy. However, 70% of TNBC patients are ineligible for immunotherapy and receive first-line chemotherapy treatment, which has modest and limited efficacy. Approximately half of patients with metastatic TNBC do not receive treatment beyond first-line chemotherapy, making it an urgent need to find new treatment options to improve clinical outcomes.

A new treatment for TNBC

To address this need, clinician-investigators from multiple centres around the world conducted the TROPION-Breast02 open-label, phase III clinical trial using Dato-DXd to treat TNBC. Dato-DXd is an ADC that delivers a potent cancer-killing drug directly to tumour cells by targeting the TROP2 protein. Currently, Dato-DXd is approved for the treatment of patients with unresectable or metastatic, hormone receptor-positive, HER2-negative breast cancer, but not TNBC.

In total, 644 TNBC patients were enrolled in TROPION-Breast02 across multiple sites across the globe including the United States, Canada, Europe, China, Korea, Japan and Singapore. Patients were randomly assigned to two treatment arms: intravenous Dato-DXd 6 mg/kg once every three weeks (323 patients) or the investigator’s choice of chemotherapy (321 patients). Patients had to be 18 and above to enrol, have locally recurrent inoperable or metastatic TNBC that was untreated, and be ineligible for treatment with immunotherapy.

Trial results showed that:

  • Progression-free survival (PFS) was significantly longer with Dato-DXd compared with chemotherapy: median PFS 10.8 months versus 5.6 months (nearly double) 
  • Overall survival (OS) was improved with Dato-DXd compared with chemotherapy: median OS 23.7 months versus 18.7 months 
  • Patients treated with Dato-DXd had an overall positive response rate to treatment of 63% compared to patients treated with chemotherapy who had an overall response rate of 29%. Median duration of response, or how long patients responded to treatment, was 12.3 months in the Dato-DXd arm and 7.1 months in the chemotherapy arm.

Dato-DXd’s most common drug-related adverse events were stomatitis (inflammation of tissue lining the mouth or lips), nausea, alopecia and neutropenia (lower levels of a type of white blood cell), whilst the most common for chemotherapy were alopecia, neutropenia and fatigue. Only 4% of patients on Dato-DXd stopped treatment due to drug-related adverse events compared to 7% of patients on chemotherapy.

What this means for TNBC patients

Not only did the trial find Dato-DXd to be an effective treatment for untreated, inoperable metastatic TNBC, but ASCENT-03, a separate, earlier phase III clinical trial of TROP2-directed ADC sacituzumab govitecan, also demonstrated improved PFS compared to chemotherapy. Combined, the results from TROPION-Breast02 and ASCENT-03 indicate that TROP2-directed ADCs are a promising class of drugs to treat TNBC.

The team is further evaluating Dato-DXd in phase III clinical trials to treat patients with Stage I-III TNBC with residual invasive disease after neoadjuvant systemic therapy, Stage II-III triple-negative or hormone receptor (HR)-low, HER2-low or -negative breast cancer and metastatic TNBC PD-L1 expressed tumours.

Dato-DXd is currently under review as first-line treatment for unresectable, metastatic TNBC by the US Food and Drug Administration and the Singapore Health Sciences Authority.

Source: National Cancer Centre Singapore

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Ultra-processed Foods Linked with Greater Risk of Overweight or Obesity in Adolescents

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The conclusion comes from a systematic review and meta-analysis of 23 studies and 155 000 adolescents across multiple countries and regions.

Photo by Erik Mclean

Adolescents who consume more ultra-processed foods (UPFs) have significantly higher odds of being overweight or obese, according to a new systematic review and meta-analysis published in the open-access journal PLOS One by Mekuriaw Nibret Aweke of the University of Gondar, Ethiopia, and colleagues. In the most recent of the analysed studies, higher UPF consumption was linked with more than twice the odds of overweight or obesity compared to lower UPF consumption.

Being overweight or obese during adolescence raises a person’s likelihood of developing type 2 diabetes, high cholesterol, hypertension, and metabolic syndrome. The increasing consumption of UPFs – defined as industrial products made largely from extracted, modified, or synthetic ingredients, and typically high in added sugars, salt, unhealthy fats, and chemical additives – represents one of the fastest-growing unhealthy eating patterns among young people worldwide.

In the new study, researchers systematically searched multiple databases for observational studies reporting on UPF consumption and weight outcomes in adolescents aged 10 through 19. They identified 23 eligible studies involving a total of 155 000 adolescents, conducted across 16 countries between 2008 and 2025.

In a meta-analysis of all 23 studies, the researchers found that adolescents with higher UPF consumption had 63% greater odds of overweight or obesity compared with those with lower intake (OR = 1.63; 95% CI: 1.36–1.95). The positive association was consistent across all geographic regions studied, including Africa, Asia, Europe, North America, and South America. Subgroup analysis by year of publication showed that the most recent studies, published in 2024 and 2025, reported the highest odds ratio (OR = 2.09), suggesting the association may be growing stronger as UPF consumption rises globally.

Among other aspects, the study is limited by its reliance on observational designs, which cannot establish causation, and by variation across studies in how UPF consumption and obesity were measured.

The authors conclude that public health strategies should prioritize reducing UPF consumption among adolescents through education, policy interventions, and promotion of minimally processed, nutrient-dense foods.

The authors add: “Higher consumption of ultra-processed foods is linked to a substantially increased risk of overweight and obesity among adolescents, emphasising the need for early dietary interventions.”

“Improving adolescent nutrition today is essential to protecting long-term population health and reducing healthcare costs associated with obesity-related conditions.”

Provided by PLOS

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Testosterone Increases Severity of Staph Skin Infections

On By ModernMedia

Study led by UTSW researchers defines how skin hormones influence bacteria and results in potential treatment for Staph infections

This laboratory image shows Staphylococcus aureus bacteria streaked in the shape of a sex steroid, like testosterone. The left shape is of wild-type S. aureus, with the lighter halo around the shape indicating haemolysis, or the breakdown of red blood cells, releasing their haemoglobin into the surrounding fluid. The right shape is a quorum-sensing mutant strain of S. aureus, which cannot damage blood cells.

Men are more susceptible than women to skin infections caused by Staphylococcus aureus bacteria, but the biological basis for this disparity has remained unclear. A new study led by UT Southwestern Medical Center researchers is the first to reveal that testosterone as a key driver of infection. The sex steroid activates a bacterial communication pathway known as quorum sensing, increasing skin cell death and promoting the destruction of red blood cells and white blood cells called neutrophils. 

Published in Nature Microbiology, the study also reported that a mirror-image form of testosterone, known as an enantiomer (ent-T), blocks quorum sensing and prevents S. aureus from damaging tissue in mouse models.

Senior author Tamia Harris-Tryon, MD, PhD, Associate Professor of Dermatology and Immunology at UT Southwestern, and first author Maria S. John, PhD, a UTSW postdoctoral researcher, have a patent pending for an ent-T-based therapeutic along with collaborators at the University of Colorado.

“This research has important implications for treating Staph skin infections and conditions complicated by Staphylococcus, such as atopic dermatitis, pemphigus, abscesses, and wound infections, including the deadliest skin infections caused by methicillin-resistant Staphylococcus aureus [MRSA],” Dr Harris-Tryon said. “It also explains why men are more susceptible to Staph infections.” 

S. aureus is the leading cause of skin infections. When it enters the bloodstream, it can cause septicaemia, a life-threatening infection that may lead to organ failure.

During infection, the bacteria use quorum sensing to detect neighbouring cells of the same species. As bacterial density rises, they produce short signalling molecules called auto-inducing peptides (AIP), which activate virulence programs and trigger toxin release, resulting in host-cell damage. 

The research team found that male skin cells consistently secrete higher levels of testosterone than female skin cells. They also found the same is true for male mice, which were significantly more susceptible to S. aureus colonisation and skin damage than female mice when exposed to a strain of MRSA. However, mice engineered to secrete less testosterone displayed greater resistance to the bacteria, while applying testosterone to the skin of female mice increased MRSA’s severity. 

In laboratory experiments, testosterone activated quorum sensing even in the absence of AIPs. Other sex steroids, including progesterone and oestrogen, had no measurable effect on quorum sensing. 

While using ent-T as an experimental control, the researchers unexpectedly identified its therapeutic potential. In lab tests, ent-T inhibited quorum sensing and reduced the bacteria’s virulence. The molecule also inhibited quorum sensing on male and female mice when applied to their skin. 

Dr Harris-Tryon won an Innovation Award from the UTSW Office for Technology Development in 2024 to fund development of an ent-T-based transdermal therapeutic for Staph.

“Our exciting finding suggests we can inhibit S. aureus virulence rather than killing the bacteria directly, an approach that prevents infection, preserves beneficial skin microbes, and reduces the selective pressure that drives antibiotic resistance while offering a potential new strategy to treat infections, including MRSA,” Dr. John said.

This work builds on Dr Harris-Tryon’s studies in 2023 and 2025 with Jeffrey McDonald, PhD, Professor in the Center for Human Nutrition and of Molecular Genetics at UTSW, which demonstrated sex-specific differences in skin hormone production. The team also has previously uncovered how the immune system stimulates testosterone production in skin cells. Dr Harris-Tryon said the current research builds on UT Southwestern’s longstanding leadership in steroid and skin hormone biology, a field in which the institution has been a global leader for decades.

Source: UT Southwestern