A research team at Saarland University has demonstrated in a clinical study that a widely used anti-allergy nasal spray containing the active ingredient azelastine can significantly reduce the risk of infection with the SARS-CoV-2 virus. The results of the placebo-controlled trial involving 450 healthy participants have now been published in JAMA Internal Medicine.
The trial, led by Professor Robert Bals, Director of the Department of Internal Medicine V at Saarland University Medical Center and Professor of Internal Medicine at Saarland University, divided the 450 participants into two groups. The treatment group of 227 individuals used an azelastine nasal spray three times a day over a 56-day period. During that same period, the 223 participants in the control group used a placebo spray three times a day. Robert Bals summarised the key finding as follows: ‘During the observation period, 2.2% of the participants in the azelastine group became infected with SARS-CoV-2; in the placebo group, it was 6.7%—three times as many.’ All infections were confirmed by PCR testing.
In addition to showing a marked reduction in coronavirus infections, the azelastine group also displayed fewer symptomatic SARS-CoV-2 infections, a lower overall number of confirmed respiratory infections, and, unexpectedly, a reduced incidence of rhinovirus infections, another major cause of respiratory illness. In the treatment group, 1.8% developed a rhinovirus infection, compared to 6.3% in the placebo group—a proportion similar to that seen for SARS-CoV-2.
Azelastine nasal spray has been available for decades as an over-the-counter treatment for hay fever. Previous in vitro studies on azelastine had already suggested antiviral effects against SARS-CoV-2 and other respiratory viruses. ‘This clinical trial is the first to demonstrate a protective effect in a real-world setting,’ says Professor Bals.
For Robert Bals, the results suggest practical applications: ‘Azelastine nasal spray could provide an additional easily accessible prophylactic to complement existing protective measures, especially for vulnerable groups, during periods of high infection rates, or before travelling.’ But Professor Bals also stressed the importance of further research: ‘Our results highlight the need for larger, multicentre trials to continue exploring the use of azelastine nasal sprays as an on-demand preventive treatment, and to examine its potential effectiveness against other respiratory pathogens.’
Besides Professor Bals, the randomised, double-blind phase 2 study ‘CONTAIN’ also involved the Institute of Clinical Pharmacy (Professor Thorsten Lehr, Dr. Dominik Selzer), the Institute of Virology (Professor Sigrun Smola), and the Saarbrücken-based pharmaceutical company URSAPHARM Arzneimittel GmbH, which sponsored the study and manufactured the investigational product. The Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) contributed through the research groups of Professor Smola and Professor Bals. The project serves as an excellent example of successful collaboration between academic research, industry partners and public health initiatives in the Saarland region.
Blood pressure matters at all ages. Children with higher blood pressure at age 7 may be at an increased risk of dying of cardiovascular disease by their mid-50s, according to preliminary research presented at the American Heart Association’s Hypertension Scientific Sessions 2025. The study is simultaneously published in JAMA.
“We were surprised to find that high blood pressure in childhood was linked to serious health conditions many years later. Specifically, having hypertension or elevated blood pressure as a child may increase the risk of death by 40% to 50% over the next five decades of an individual’s life,” said Alexa Freedman, Ph.D., lead author of the study and an assistant professor in the department of preventive medicine at the Northwestern University’s Feinberg School of Medicine in Chicago. “Our results highlight the importance of screening for blood pressure in childhood and focusing on strategies to promote optimal cardiovascular health beginning in childhood.”
Previous research has shown that childhood blood pressure is associated with an increased risk of cardiovascular disease in adulthood, and a 2022 study found that elevated blood pressure in older children (average age of 12 years) increased the risk of cardiovascular death by middle age (average age of 46 years). The current study is the first to investigate the impact of both systolic (top number) and diastolic (bottom number) blood pressure in childhood on long-term cardiovascular death risk in a diverse group of children. Clinical practice guidelines from the American Academy of Pediatrics recommend checking blood pressure at annual well-child pediatric appointments starting at age 3 years.
“The results of this study support monitoring blood pressure as an important metric of cardiovascular health in childhood,” said Bonita Falkner, MD, FAHA, an American Heart Association volunteer expert. “Moreover, the results of this study and other older child cohort studies with potential follow-up in adulthood will contribute to a more accurate definition of abnormal blood pressure and hypertension in childhood.” Falkner, who was not involved in this study, is emeritus professor of paediatrics and medicine at Thomas Jefferson University.
The researchers used the National Death Index to follow up on the survival or cause of death as of 2016 for approximately 38,000 children who had their blood pressures taken at age 7 years as part of the Collaborative Perinatal Project (CPP), the largest US study to document the influence of pregnancy and post-natal factors on the health of children. Blood pressure measured in the children at age 7 years were converted to age-, sex-, and height-specific percentiles according to the American Academy of Pediatrics clinical practice guidelines. The analysis accounted for demographic factors as well as for childhood body mass index, to ensure that the findings were related to childhood blood pressure itself rather than a reflection of children who were overweight or had obesity.
After follow-up through an average age of 54 years, the analysis found:
Children who had higher blood pressure (age-, sex-, and height-specific systolic or diastolic blood pressure percentile) at age 7 were more likely to die early from cardiovascular disease as adults by their mid-50s. The risk was highest for children whose blood pressure measurements were in the top 10% for their age, sex and height.
By 2016, a total of 2,837 participants died, with 504 of those deaths attributed to cardiovascular disease.
Both elevated blood pressure (90-94th percentile) and hypertension (≥ 95th percentile) were linked with about a 40% to 50% higher risk of early cardiovascular death in adulthood.
Moderate elevations in blood pressure were also important, even among children whose blood pressure was still within the normal range. Children who had blood pressures that were moderately higher than average had a 13% (for systolic) and 18% (for diastolic) higher risk of premature cardiovascular death.
Analysis of the 150 clusters of siblings in the CPP found that children with the higher blood pressure at age 7 had similar increases in risk of cardiovascular death when compared to their siblings with the lower blood pressure readings (15% increase for systolic and 19% for diastolic), indicating that their shared family and early childhood environment could not fully explain the impact of blood pressure.
“Even in childhood, blood pressure numbers are important because high blood pressure in children can have serious consequences throughout their lives. It is crucial to be aware of your child’s blood pressure readings,” Freedman said.
The study has several limitations, primarily that the analysis included one, single blood pressure measurement for the children at age seven, which may not capture variability or long-term patterns in childhood blood pressure. In addition, participants in the CPP were primarily Black or white, therefore the study’s findings may not be generalisable to children of other racial or ethnic groups. Also, children today are likely to have different lifestyles and environmental exposures than the children who participated in the CPP in the 1960s and 1970s.
Study details, background and design:
38 252 children born to mothers enrolled at one of 12 sites across the U.S. as part of the Collaborative Perinatal Project between 1959-1965. 50.7% of participants were male; 49.4% of mothers self-identified as Black, 46.4% reported as white; and 4.2% of participants were Hispanic, Asian or other groups.
This analysis reviewed blood pressure taken at age 7, and these measures were converted to age-, sex-, and height-specific percentiles according to the American Academy of Pediatrics Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents.
Survival through 2016 and the cause of death for the offspring of CPP participants in adulthood were retrieved through the National Death Index.
Survival analysis was used to estimate the association between childhood blood pressure and cardiovascular death, adjusted for childhood body mass index, study site, and mother’s race, education and marital status.
In addition, the sample included 150 groups of siblings, and the researchers examined whether the sibling with higher blood pressure was more likely to die of cardiovascular disease than the sibling with lower blood pressure. This sibling analysis allowed researchers to ask how much shared family and early childhood factors might account for the mortality risk related to blood pressure.
The health department has plans to roll out lenacapavir, a twice-yearly HIV prevention injection, in a select group of public sector clinics by April 2026. Meanwhile, little progress has been made towards rolling out a two-monthly prevention injection, despite the four-year head start this product had on lenacapavir.
Injections that provide months of protection at a time against HIV infection have been hailed by several leading experts as game-changers with the potential to help end the HIV epidemic.
The two antiretroviral-containing injections leading the field are long-acting cabotegravir (CAB-LA) and lenacapavir. Both have been shown to effectively eliminate the risk of contracting HIV in large clinical trials. The main difference between the two shots is that CAB-LA provides two months of protection at a time, while lenacapavir provides six.
CAB-LA captured global attention back in 2020 when pivotal trial results showed that the two-monthly injection was more effective than daily prevention pills in preventing HIV infection. Lenacapavir was thrust into the spotlight four years later in 2024 when two large trials demonstrated that the twice-yearly injection provided almost perfect protection against HIV.
There are still no clear plans for providing CAB-LA in South Africa’s public sector clinics, despite the four-year head start that it had on lenacapavir. By contrast, lenacapavir injections could be available in some select public sector clinics by April of next year, according to reporting by Bhekisisa.
How CAB-LA fell behind
In July 2022, the World Health Organization (WHO) recommended CAB-LA as a tool to prevent HIV and by December 2022 it was registered for use in South Africa.
In February 2023 though, South Africa’s National Essential Medicines Committee stated that it could not recommend the use of CAB-LA in the country because the medicine’s manufacturer, ViiV Healthcare, had yet to share how much it would charge the country for the shots.
It was only in late 2023 that ViiV provided pricing details for public sector procurement in certain low-and middle- income countries, including South Africa. That price was around R540 ($30) per dose or R3 240 ($180) per person per year, which the health department said was unaffordable for the country.
The price has since dropped slightly to around R2 880 ($160) per person per year, Mitchell Warren, from the US-based HIV advocacy organisation AVAC, told Spotlight.
In 2024, the health department requested further details from ViiV on its CAB-LA pricing but there is no indication that any progress has been made towards securing a lower price and enabling local procurement of CAB-LA for public sector facilities.
Khadija Jamaloodien, the top official for health products procurement in the National Department of Health, told Spotlight the department could not comment on whether there have been any developments towards local procurement of CAB-LA.
A spokesperson for ViiV told Spotlight: “We have not received any orders to date for CAB-LA for PrEP to supply to South Africa”. PrEP, or pre-exposure prophylaxis, refers to taking an injection to prevent HIV infection.
What about CAB-LA in the private sector?
For those using private healthcare in South Africa, CAB-LA also remains inaccessible. ViiV has not launched CAB-LA in the private sector or disclosed the price at which it will sell CAB-LA through private pharmacies.
ViiV did not respond to Spotlight’s questions regarding its plans and timelines for launching CAB-LA in the country’s private sector.
PEPFAR steps in, but doesn’t deliver
After the health department balked at ViiV’s CAB-LA price for the public sector, the United States President’s Emergency Plan for AIDS Relief (PEPFAR) announced plans to kick start the rollout of CAB-LA in South Africa and some other African countries.
PEPFAR pledged to buy CAB-LA from ViiV for donation to ten African countries during 2024 and 2025. The largest donation of 231 000 CAB-LA doses was designated for South Africa.
While some of the PEPFAR-donated stock began reaching countries before the Trump administration halted foreign aid on 20 January, according to Warren, South Africa never received any of the promised doses.
These donations are no longer expected, given cuts to the agency’s capacity and budget under the Trump administration.
The US State Department did not respond to Spotlight’s questions seeking confirmation that the CAB-LA donations would no longer be delivered, but our health department told Spotlight it doesn’t expect to receive this donation.
Gilead leapfrogs ViiV
Amid the delays and uncertainty surrounding CAB-LA’s pricing and rollout, Gilead, the company that manufactures lenacapavir, has positioned their product to become the first long-acting injectable form of HIV prevention available at any real scale in South Africa.
While lenacapavir is not yet registered in South Africa, Hasina Subedar, the senior technical advisor for HIV prevention in the National Department of Health, told Bhekisisa that it plans to start rolling out lenacapavir in 300 public clinics by April 2026 – less than 10% of the well over 3000 clinics in the country.
SAHPRA authorisation is expected to be granted in the coming months, as lenacapavir has already been recommended for marketing authorisation through the EU medicines for all (EU-M4All) initiative – a process which includes regulators from South Africa. In addition to securing local registration, lenacapavir must also receive a positive recommendation from South Africa’s National Essential Medicines List Committee to enable its rollout.
Gilead has secured a deal with the Global Fund for HIV, TB and Malaria, as well as private donors, that will allow lenacapavir to be rolled out in eight African countries, including in South Africa at a cost to country of R1080 ($60) per person per year.
Under this deal, private donations from the Children’s Investment Fund Foundation (CIFF) will also contribute toward procurement of lenacapavir. CIFF contributions will be above and beyond the $60 contributed by countries per person per year.
While the amount that Gilead will recoup for a year’s supply of lenacapavir under the deal has not been disclosed, it is speculated to be between R1800 ($100) and R2 160 ($120), according to Warren.
He added that Gilead’s deal with the Global Fund will allow countries to begin budgeting and planning for lenacapavir’s rollout using Gilead’s product while they await availability of more affordable generic products in a few years’ time.
The lack of transparency around Gilead’s pricing is uncommon in South Africa, which has strong legal requirements for medicine price transparency. Despite transparency concerns, the National Department of Health has indicated that they will participate in Gilead’s Global Fund arrangement.
By keeping the price secret, two advocacy groups, the Health Justice Initiative and Health Gap, have argued that the deal will undermine efforts in countries not included in the arrangement to negotiate and secure affordable pricing of lenacapavir.
Are HIV prevention injections cost effective for South Africa?
Local researchers have crunched the numbers to establish whether CAB-LA and lenacapavir offer good value for money.
These analyses compared the cost-effectiveness of HIV injections to the widely available prevention pills in public clinics, Lise Jamieson, senior researcher at WITS HE2RO, told Spotlight
The prevention pills provided by the National Department of Health are purchased for R1000 per person per year, said Jamaloodien.
Jamieson said that, according to modelling, prevention injections will avert more HIV infections than prevention pills. Generally speaking, products that provide protection for longer periods are more effective since their efficacy is less dependent on people regularly taking pills or going to the clinic to get an injection. We can thus accept a higher price for lenacapavir (providing six month of protection) than for CAB-LA (only two months of protection) because modelling indicates that this product will avert more HIV infections and delivers more treatment cost savings over time.
Jamieson said according to the latest iteration of their cost-effectiveness modelling, which has not yet been published, CAB-LA needs to be capped around R1800 ($100) per person per year to be cost effective, while lenacapavir needs to be capped around R3600 ($170) per person per year.
Based on this analysis, for South Africa to roll out lenacapavir at $60 per person per year is highly cost-effective, while buying CAB-LA at $160 per person per year is not cost-effective.
Lenacapavir use also requires fewer clinic visits per year than CAB-LA (two versus six) which places less of a strain on health facilities and providers.
Cheaper generic versions of lenacapavir and CAB-LA are expected to become available in 2027.
Lenacapavir generics, Warren said, are expected to enter the market around the same time as generic CAB-LA despite CAB-LA’s initial head start. This is because Gilead was quicker to license generic manufacturers and used a faster licensing approach than ViiV, he added.
Compared to CAB-LA, Warren said it would be faster to show that the generic version of lenacapavir works the same as the original – a necessary step before generic products can be approved. Added to this, he noted that generic companies would likely move faster to bring lenacapavir to market because buyers showed more interest in it.
How will procurement of lenacapavir be funded?
While lenacapavir is cost effective for South Africa at $60 per person per year, purchasing it may nevertheless be challenging given the country’s tight healthcare budget.
HIV prevention pills are procured domestically in South Africa, but Jamieson said the country will need additional funds or donor support to roll out lenacapavir.
The National Department of Health and the Global Fund agreed to allocate R520 million of the country’s Global Fund grant towards buying lenacapavir, Bhekisisa reported in July. This allocation will allow more than 450 000 people in the country to access lenacapavir over the next three years.
Can lenacapavir turn the tide on the epidemic?
In addition to looking at the cost-effectiveness of long acting injectables, Jamieson and her colleagues have modelled how the rollout of injectable HIV prevention options will impact new HIV infections in the country.
Jamieson said if South Africa initiates roughly 1 million people on lenacapavir over the next year and then increase access to reach 4 million people in the next 20 years, HIV incidence could fall below 0.1% by 2038 – with a projected 3.5 million people on lenacapavir by then. At this level, the country would effectively end the HIV epidemic.
Scaling up lenacapavir to this level will require significant political will and additional investment above and beyond what has already been committed by the Global Fund.
Meanwhile, researchers are working on new versions of lenacapavir and CAB-LA that could double the length of protection offered by each.
As Spotlight previously reported, there are promising signs for a lenacapavir formulation that could provide 12 months of protection as opposed to the current six, and a CAB-LA formulation that could provide four months of protection rather than two. HIV prevention tablets that provide a month of protection at a time are also under development. It however remains to be seen whether these new formulations will succeed in the pivotal clinical trials testing their safety and effectiveness.
AI-based medicine will revolutionise care including for Alzheimer’s and diabetes, predicts a technology expert, but it must be accessible to all patients
AI image created with Gencraft
Healing with Artificial Intelligence, written by technology expert Daniele Caligiore, uses the latest science research to highlight key innovations assisted by AI such as diagnostic imaging and surgical robots.
From exoskeletons that help spinal injury patients walk to algorithms that can predict the onset of dementia years in advance, Caligiore explores what he describes as a ‘revolution’ that will change healthcare forever.
Economically, the market for AI in healthcare is experiencing rapid growth, with forecasts predicting an increase in value from around USD 11 billion in 2021 to nearly USD 188 billion by 2030, reflecting an annual growth rate of 37%. AI is already being used in some countries, for example to search through genetic data for disease markers, or to assist with scheduling and other administrative tasks – and this trend is set to continue.
However, the author caveats his predictions of progress by warning these technologies may widen existing inequality. Caligiore suggests that AI-based medicine must be available to all people, regardless of where they live or how much they earn, and that people from low-income nations must not be excluded from cutting-edge care which wealthier nations can access.
Other challenges posed by the advancement of AI in healthcare includes who takes responsibility for treatment decisions, especially when a procedure goes wrong. This is a particular challenge given widespread concerns around explainable AI, as many advanced AI systems operate as black boxes, making decisions through complex processes that even their creators cannot fully understand or explain.
Caligiore says AI should support doctors and patients, not replace doctors who, says the author, have a ‘unique ability to offer empathy, understanding, and emotional support’.
“AI should be viewed as a tool, not a colleague, and it should always be seen as a support, never a replacement,” writes Caligiore.
“It is important to find the right balance in using AI tools, both for doctors and patients. Patients can use AI to learn more about their health, such as what diseases may be associated with their symptoms or what lifestyle changes may help prevent illness. However, this does not mean AI should replace doctors.”
Despite his warnings, Caligiore is largely optimistic about the impact of AI in healthcare: “Like a microscope detecting damaged cells or a map highlighting brain activity during specific tasks, AI can uncover valuable insights that might go unnoticed, aiding in more accurate and personalized diagnoses and treatments,” he says.
In any case, Caligiore predicts the healthcare landscape will look ‘dramatically different’ in a few years, with technology acting as a ‘magnifying glass for medicine’ to enable doctors to observe the human body with greater precision and detail.
Examples of where AI will make profound impacts in healthcare include, regenerative medicine, where gene and stem cell therapies repair damaged cells and organs. Spinal cord injury patients are among those who could benefit.
AI may also provide personalised therapies, suggesting treatments tailored to specific individuals often based on their unique genetic profile. Studies are being conducted into targeting different tremor types in Parkinson’s and breast cancer subtypes
The convergence of regenerative medicine, genetically modified organisms (GMOs), and AI is the next frontier in medicine, Caligiore suggests. Genetically modified organisms (GMOs), living organisms whose genetic material has been altered through genetic engineering techniques, have already paved the way for personalised gene therapies.
Blending real and virtual worlds may also prove useful to healthcare, for example the ‘metaverse’ – group therapy where patients participate with an avatar, or ‘digital twins’ – AI simulations of a patient’s body and brain on a computer so doctors can identify underlying causes of disease and simulate the effects of various therapies for specific patients to help doctors make more informed decisions.
These advances and others will reshape the doctor-patient relationship, according to Healing with Artificial Intelligence, but the author suggests the key is for patients and clinicians to keep a critical mindset about AI.
Caligiore warns that role of physicians will evolve as AI becomes more integrated into healthcare but the need for human interactions will remain ‘central to patient care’.
“While healthcare professionals must develop technical skills to use AI tools, they should also nurture and enhance qualities that AI cannot replicate – such as soft skills and emotional intelligence. These human traits are essential for introducing an emotional component into work environments,” he explains.
Ethical patient record keeping is essential to modern healthcare, ensuring safe, effective, and trustworthy care. Accurate documentation supports continuity, clinical decision-making, and legal accountability, while also carrying ethical importance by safeguarding sensitive information with honesty, confidentiality, and respect. Poor record keeping can decrease patient outcomes, create confusion, impact multidisciplinary collaboration, and create legal risk.
Managing records ethically protects patient privacy and autonomy while allowing patients access and control over their health data. With the growth of digital health technologies, new challenges such as data security, electronic informed consent, and cybersecurity have emerged. Breaches or cyberattacks can erode trust, discourage information sharing, and disrupt care delivery, highlighting the need to balance accessibility with strong safeguards.
Join our expert speaker panel to explore how you can effectively manage your patient records to ensure integrity and continue to build trust vital to patient-centred healthcare.
During this webinar, attendees will review the HPCSA Booklet 9:Guidelines on the keeping of patient health records where the pertinent South Africa laws and basic principles around ethical practices for maintaining patient health records are laid out. The webinar will offer insights into both paper and electronic record-based practices.
The audience will have an opportunity to engage with faculty who offer insights from a clinical, legal, medical malpractice insurance, cybersecurity, and medical practice setup and management perspective through short lectures, interactive case studies, a series of multiple choices questions and Q&A sessions.
This webinar will focus on specialist practices. Administrative staff working in these practices are welcome to join the discussion.
In this month’s podcast, QuickNews looks at a new Lancet study, “Non-autoimmune, insulin-deficient diabetes in children and young adults in Africa.” In this study, researchers report that a significant subset of what has previously been classified as Type 1 diabetes in sub-Saharan Africa may in fact be a distinct, novel form of the disease.
The individuals in this subset did not exhibit the typical autoimmune markers (islet autoantibodies) usually found in classic Type 1 diabetes in other parts of the world. The researchers instead identified a novel, non-autoimmune, insulin-deficient subtype of diabetes that is also distinct from Type 2 diabetes.
Further evidence of this new subtype was found in Black individuals in the USA, albeit less frequently, but not in White individuals. The discovery throws a spotlight on the heterogeneity of diabetes diagnoses in sub-Saharan Africa, and points to the need to consider alternative causes and explore new prevention and treatment strategies for this distinct form of the disease.
The placenta has long been thought to produce serotonin during pregnancy. But in a new study, Yale researchers shatter the deep-rooted hypothesis – and show that the placenta doesn’t produce serotonin but instead regulates its delivery to the embryo and foetus. They found that serotonin comes from the pregnant parent, with the placenta acting as a “serotonin shield” that controls how much reaches the embryo and foetus.
The findings, published in the journal Endocrinology, could offer critical insights into how a parent’s serotonin levels might affect the development of their baby’s body and brain, the researchers say.
“The placenta is in essence the ‘serotonin shield’ that regulates how much serotonin is ultimately delivered to the embryo and foetus, not the source of serotonin,” said Harvey Kliman, a research scientist in the Department of Obstetrics, Gynecology, and Reproductive Sciences at Yale School of Medicine and corresponding author of the study. “Why does this matter? Because now we correctly know where this delivery is regulated.”
Often called a “happiness hormone,” serotonin regulates mood, so it’s often associated with the brain. In reality, less than 5% of serotonin is made in the brain, with 95% of it made in the gut. But serotonin does more than just regulate mood. It’s also a growth hormone. In the gut, it gets taken up by platelets and is delivered to parts of the body that need to grow, including in wound healing.
During pregnancy, serotonin also helps with growth: It travels into the placenta through a special protein known as the serotonin transporter (SERT) where it plays a critical role in the development of the embryo and foetus.
Serotonin from the mother is taken up by the foetal placenta, which then produces a myriad of hormones, growth factors, and regulators that are delivered to the foetus.
For the new study, researchers sought to better understand these relationships by using a pure source of placenta cells, unlike in previous studies that looked at either whole animals or isolated mouse placentas. To do so, they first purified human cytotrophoblasts, which are the stem cells that make all the cells of the placenta. They then added serotonin to those cells to see where it would go and discovered it concentrated in the nucleus. Next, they used a selective serotonin reuptake inhibitor (SSRI) that blocked SERT, escitalopram, to show that the normal growth, function, and differentiation of these cells was completely blocked.
They also used another inhibitor called cystamine to block serotonylation, or the process by which serotonin is added to proteins like histone 3, which turns genes “on” and “off.” Again, that completely blocked the normal growth of the cells.
Blocking either SERT or serotonylation led to significant changes in gene expression of RNAs in the cytotrophoblasts, they found. Some genes, including ones involved in making, moving, and growing cells, became downregulated, or less active, when serotonin couldn’t enter the cell. Other gene, including ones that help cells stay alive and protect them, became upregulated, or more active. According to the researchers, these findings show that serotonin is critical for the growth of the cytotrophoblasts, the placenta, and by extension, the foetus.
Additionally, researchers discovered that the cytotrophoblasts don’t contain tryptophan hydroxylase (TPH-1), or the enzyme that makes serotonin, indicating the cells within the placenta can’t produce serotonin on their own.
“This suggests that factors that either inhibit serotonin transport through the placenta, or increase it, may have a significant impact on the placenta, embryo, foetus, and ultimately, the newborn and its brain,” Kliman said.
For example, Kliman says this explains why taking SSRIs, which decrease the levels of serotonin into the placenta, leads to smaller babies, and why, conversely, increased levels of serotonin may lead to bigger babies, with bigger brains, who may be at increased risk for developmental disabilities like autism.
Kliman and his lab have long investigated the link between placentas and children with autism, specifically the number of trophoblast inclusions (TIs) in the placenta. TIs are like wrinkles or folds in the placenta, caused by cells multiplying more than they should, typically only seen in pregnancies where there are genetic problems with the foetus.
This new study is the culmination of research first published in 2006 that found significantly more TIs in the placentas from children with autism, and later in 2021, that the genetics of the foetus, and not the parent’s uterine environment, determine how many TIs are in the placenta.
“This puts a big nail into the theory that vaccines cause autism,” suggested Kliman. “Autism, in essence, starts in the womb, not after delivery, and is most likely due to the genetics of the placenta and to a lesser extent, the maternal environment the placenta finds itself in.”
Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health
About a dozen studies in the past five years have made claims linking nearly every type of human cancer with the presence of microbiomes, “communities” of bacteria, viruses and fungi that live in or on peoples’ bodies. Now, scientists at Johns Hopkins Medicine say a study that sequenced human cancers found far less microbial DNA sequences than earlier studies reported in the same cancer tissue samples.
“It’s the nature of science to validate, confirm and reproduce findings,” says Steven Salzberg, PhD, Professor of Biomedical Engineering, Computer Science, and Biostatistics at The Johns Hopkins University. “Over time, we see a more complete picture of new research, and in this case, we did not find any associations between microbiomes and many types of cancer.”
Salzberg says details of the new study, published Sept. 3 in Science Translational Medicine, surveyed the whole genome sequences generated from 5734 tissue samples collected from 25 cancer types and stored in a large National Cancer Institute-funded database, The Cancer Genome Atlas (TCGA). About half of the samples are from normal tissues and blood, the other half from solid tumours and blood-based cancers.
The TCGA’s whole genome sequencing data contains millions of chopped up pieces of DNA molecules, known as reads, from each tissue sample. The original goal of the TCGA studies was to identify mutations in the DNA sequence of genes that might be associated with various cancer types. Sometimes, though, the original tumors might have microbes in them, and the reads could be used to identify those microbes.
Because reads often contain contaminants from bits of DNA left behind in sequencing machinery or picked up from the air or surfaces, samples can acquire DNA from those sources, as well as from the original tumour tissues. Salzberg says extraordinary efforts were made to identify such contaminants, preventing their study from displaying false results.
To rule out contaminants, Salzberg and his team relied on extensive experience with genomic sequencing and careful analysis of control samples to identify reads belonging to sequences known or highly likely to have contaminated samples.
For the current study, a continuation of one that the Johns Hopkins team published in 2023, Salzberg and first author Yuchen “Peter” Ge, a graduate student in biomedical engineering at Johns Hopkins, removed human DNA sequences from the TCGA data sets by mapping each read against two human reference genomes – one from the Telomere-to-Telomere (T2T) project and another from the Genome Reference Consortium.
After removing human DNA, the research team was left with, on average, 2.4 million reads per sample, or about 0.35% of the total 6.5 billion tumour sample reads. Of these, the research team found 323 million human DNA reads that weren’t eliminated in the first pass and 986 million reads they classified as contaminants.
They next compared the remaining sequencing reads against a database containing 50 651 genomes representing 30,355 species of bacteria, viruses, fungi and archaea (single-celled organisms that aren’t bacteria or viruses).
After removing human DNA sequences and contaminants, the average proportion of microbial DNA reads in solid tumour samples was 0.57% and 0.73% in blood cancers.
The Johns Hopkins researchers then compared their new results to a study published five years ago in the journal Nature [since retracted, because of concerns about contaminants in the microbial data], and found the previous study identified 56 times as many microbial reads as the new study for half of the total microbial reads. And 5% of the time, the previous study found 9,000 times the number of microbial reads as the current Johns Hopkins study. Salzberg says the microbial reads in the retracted study were highly likely to be contaminants.
“This disparity in the number of microbial reads didn’t occur in just a few samples,” says Salzberg. “Over the whole study, the previous researchers found far more microbial reads than we did.”
In another comparison of a study published in Cell in 2022 and the current Johns Hopkins work, the 2022 study reported fungal DNA amounts that were hundreds of times more than what was found in the current Johns Hopkins study, largely due to contaminants.
Among the DNA samples in the current Johns Hopkins study, in which they did find microbiome DNA, the researchers found microbes that have long been linked with human cancer, such as HPV (linked with cervical and some head and neck cancers), Helicobacter pylori (linked to stomach cancer), and Fusobacterium nucleatum and Bacteroides fragilis (linked with GI cancers).
The current Johns Hopkins study and the previous ones published in Cell and Nature reported microbiomes of Saccharomyces cerevisiae, commonly known as baker’s yeast. “It’s one of the most common contaminants in sequencing labs,” says Salzberg. They also found a virus that infects plant fungi, Rosellinia necatrix partitivirus 8, which has no known link to human disease.
Salzberg said the need to carefully document claims about the links between cancer and microbiomes is “especially important” as efforts ramp up to diagnose cancers early using microbiome information.
The Johns Hopkins researchers have made their sequencing analysis data available online to other scientists in the supplementary materials in Science Translational Medicine and online.
Scientists are investigating a small region of the brain that plays a major role in memory, spatial navigation, and perhaps Alzheimer’s disease. One of the first parts of the brain affected by Alzheimer’s disease is the entorhinal cortex – a region that plays a big role in memory, spatial navigation, and the brain’s internal mapping system.
With support announced in September from the Commonwealth of Virginia’s Alzheimer’s and Related Diseases Research Award Fund, Virginia Tech scientists Sharon Swanger and Shannon Farris are working to understand why this area is especially vulnerable.
Swanger studies how brain cells communicate across synapses, while Farris focuses on how memory at the molecular level. Their overlapping expertise made the collaboration a natural fit.
“We’ve both been studying for a while,” said Swanger, assistant professor at the Fralin Biomedical Research Institute at VTC. “This new collaborative project brings together my work on synapses and Shannon’s on mitochondria in a way that addresses a big gap in the field.”
“This kind of state-level support is critical,” said Farris, also an assistant professor at the research institute. “It gives researchers in Virginia the chance to ask questions that may eventually make a difference for people living with Alzheimer’s. It’s meaningful to be part of research that could help people facing that journey.”
A key focus of their research is mitochondria – tiny structures inside brain cells that provide the energy needed for a variety of cellular functions in neurons including transmission. In Alzheimer’s disease, mitochondria stop working properly early in the course of the disease.
Farris and Swanger are investigating whether mitochondria in a vulnerable memory-related circuit may become overloaded with calcium, a key signaling chemical for multiple neuronal and synaptic processes. That overload could contribute to the early breakdown of memory.
“The connection between these cells is one of the first to fail in Alzheimer’s,” Farris said. “We found that this synapse has unusually strong calcium signals in nearby mitochondria – so strong we can see them clearly under a light microscope. Those kinds of signals are hard to ignore. It gives us a model where we can really watch what’s happening as things start to go wrong.”
To test their hypothesis, the researchers will study brain tissue from healthy mice and mice with Alzheimer’s. By comparing how mitochondria function and how brain cells communicate across synapses in each group, they hope to find early signs of stress or failure in the entorhinal cortex–hippocampus circuit.
People who take medication for ADHD have a lower risk of suicide attempts, substance abuse, traffic accidents, and criminality than people with ADHD who do not take medication. This is shown in a new study by researchers from Karolinska Institutet and University of Southampton, published in the journal BMJ.
ADHD, which affects about 5% of children and 2.5% of adults globally, is associated with an increased risk of suicide attempts, substance abuse, accidents, and crime, among other things.
The researchers behind the study wanted to investigate whether ADHD medication reduces the risk of these outcomes by analysing Swedish national registry data between 2007 and 2020.
A total of nearly 150 000 individuals between the ages of 6 and 64 with newly diagnosed ADHD were included. The average age in the group was 17, and 41% were women. Of these, 57% started medication, with methylphenidate being the most common drug.
The researchers compared people who had started medication within three months of diagnosis with those who had not, and assessed the outcomes over two years after diagnosis.
Reduction in the risk of serious outcomes
The results showed that ADHD medication was associated with a significant reduction in the risk of several serious outcomes: suicide attempts decreased by 17%, substance abuse by 15%, traffic accidents by 12%, and criminality by 13%. The effects were even more pronounced in certain subgroups – for example, a 25% reduction in substance abuse and criminality was noted in individuals who had had recurring problems with these issues.
One possible explanation is that the medication leads to reduced impulsivity, which can reduce the risk of crime by curbing aggressive behaviour, as well as improved attention, which can reduce the risk of traffic accidents by reducing distractions,” says the study’s last author, Zheng Chang, a researcher at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. He continues:
“These results provide evidence that ADHD medication can affect important health and societal outcomes, which should be taken into account both in clinical practice and in the public debate on drug treatment.”
The study is a collaboration between Karolinska Institutet and the University of Southampton. The study was funded by the Swedish Research Council and the Swedish Research Council for Health, Working Life and Welfare, Forte, among others. Some researchers have received fees from pharmaceutical companies, but for work outside the current study.
