Day: March 5, 2024

Categories : Obstetrics & GynaecologyTags :

New Study Links Placental Oxygen Levels to Foetal Brain Development

On By ModernMedia
Image by Scientific Animations CC4.0

A new study published in JAMA Network Open shows oxygenation levels in the placenta, formed during the last three months of foetal development, are an important predictor of cortical growth and is likely a predictor of childhood cognition and behaviour.

“Many factors can disrupt healthy brain development in utero, and this study demonstrates the placenta is a crucial mediator between maternal health and foetal brain health,” said Emma Duerden, Canada Research Chair in Neuroscience & Learning Disorders at Western University, Lawson Health Research Institute scientist and senior author of the study.

The connection between placental health and childhood cognition was demonstrated in previous research using ultrasound, but for this study, Duerden, research scientist Emily Nichols and an interdisciplinary team of Western and Lawson researchers used magnetic resonance imaging (MRI), a far superior and more holistic imaging technique. This novel approach to imaging placental growth allows researchers to study neurodevelopmental disorders very early on in life, which could lead to the development of therapies and treatments.

“While ultrasound provides some measure of placental function, it is imprecise and prone to error, so MRI is just a bit more specific and precise,” said Nichols, lead author of the study. “You wouldn’t use MRI necessarily to diagnose placental growth restriction, you would use ultrasound, but MRI gives us a much better way to understand the mechanisms of the placenta and how placental function is affecting the foetal brain.”

The study was led by Duerden and Nichols and co-authored by researchers from the Faculty of Education, Schulich School of Medicine & Dentistry, Western Engineering and Lawson Health Research Institute.

The placenta, an organ that develops in the uterus during pregnancy, is the main conduit for oxygenation and nutrients to a fetus, and a vital endocrine organ during pregnancy.

“Anything a foetus needs to grow and thrive is mostly delivered through the placenta so if there is anything wrong with the placenta, the foetus might not be receiving the nutrients or the levels of oxygenation it needs to thrive,” said Nichols.

Poor nutrition, smoking, cocaine use, chronic hypertension, anaemia, and diabetes may result in foetal growth restriction and may cause problems for the development of the placenta. Foetal growth restriction is relatively common and happens in about six per cent of all pregnancies and globally impacts 30 million pregnancies each year.

“There can be many issues related to the healthy development of the placenta,” said Duerden. “If it does not develop properly, the foetal brain may not get enough oxygen and nutrients, which may affect childhood cognition and behaviour.”

Impact, affect and change

The study revealed that a healthy placenta in the third trimester particularly impacts the cortex and the prefrontal cortex, regions of the child’s brain that are important for learning and memory.

“An unhealthy placenta can place babies at risk for later life learning difficulties, or even something more serious, like a neurodevelopmental disorder,” said Duerden. “This research can open a lot of doors as we still don’t really understand everything there is to know about the placenta. We are just scratching the surface.”

The study, funded by grants from Brain Canada, The Children’s Health Research Institute, Canadian Institutes of Health Research, BrainsCAN and the Molly Towell Perinatal Research Foundation, is also an important first step in biomarking the impact of oxygenation levels in the placenta and considering changes for expectant mothers to deal with less-than-ideal placental conditions.

While oxygenation in the placenta in the third trimester predicts foetal cortical growth (development of the outermost layer of the brain – the cerebral cortex), results of the study indicate it may not affect subcortical maturation, or the deep grey and white matter structures of the brain.

Subcortical structures in the brain, responsible for children’s temperament or motor functions such as the amygdala and basal ganglia, may be more vulnerable to factors affecting the placenta in the second trimester.

“We now have a better understanding of how the placenta affects the cortex. With this basic knowledge, we now have an idea of how these two things are related and we can identify or benchmark healthy levels that lead to brain cortical growth,” said Nichols. “The subcortical regions of the brain appear to be unaffected by placental growth, at least in the healthy samples from our study.”

Duerden, Nichols, and the team scanned pregnant women twice (during their third trimester) for the study at Western’s Translational Imaging Research Facility.

“This is one of the few datasets in the world where there are two scans collected in utero during the third trimester. There are not many groups in the world doing foetal MRI, so it is a super-rich data set that allows us to look at growth over time,” said Duerden. “Western is probably one of the few places where we can do the research because we have the expertise and the facilities to do it.”

Source: University of Western Ontario

Categories : Cardiovascular DiseaseTags :

Heart Disease Research Challenges ‘One Size Fits All’ Aspirin Guidelines

On By ModernMedia

Analysis of results from international trials question whether current aspirin recommendations apply to all patients

Photo by cottonbro studio

Heart disease researchers have identified a group of patients in whom international guidelines on aspirin use for heart health may not apply. In a study published in the medical journal Circulation, the findings of a review of data from three clinical trials challenge current best practice for use of the drug for primary prevention of heart disease or stroke – otherwise known as atherosclerotic cardiovascular disease.

The research examined the results from clinical trials involving more than 47 000 patients in 10 countries, including the US, the UK and Australia, which were published in 2018.

The analysis focused on findings for a subgroup of 7222 patients who were already taking aspirin before the three trials commenced. Those studied were at increased risk for cardiovascular disease and were taking aspirin to prevent the first occurrence of a heart attack or stroke.

The data showed a higher risk of heart disease or stroke – 12.5% versus 10.4% – for patients who were on aspirin before the trials and who then stopped, compared to those who stayed on the drug.

Analyses also found no significant statistical difference in the risk for major bleeding between the two groups of patients.

The research was led by Professor J. William McEvoy, Established Professor of Preventive Cardiology at University of Galway and Consultant Cardiologist at Saolta University Health Care Group, in collaboration with researchers in University of Tasmania and Monash University, Melbourne.

Professor McEvoy said: “We challenged the notion that aspirin discontinuation is a one-size-fits-all approach.”

The research team noted results from observational studies which suggest a 28% higher risk of heart disease or stroke among adults who were prescribed aspirin to reduce the risk for a first heart attack or stroke, but who subsequently chose to stop taking the aspirin without being told to do so by their doctor.

Based in large part on three major clinical trials published in 2018, international guidelines no longer recommend the routine use of aspirin to prevent the first occurrence of heart attack or stroke.

Importantly, aspirin remains recommended for high-risk adults who have already had a heart disease or stroke event, to reduce the risk of a second event.

The move away from primary prevention aspirin in recent guidelines is motivated by the increased risk of major bleeding seen with this common medication in the three trials, albeit major bleeding is relatively uncommon on aspirin and was most obvious only among trial participants who were started on aspirin during the trial, rather than those who were previously taking aspirin safely.

These trials primarily tested the effect of starting aspirin among adults who have not previously been treated with the drug to reduce the risk of atherosclerotic cardiovascular disease. Less is known about what to do in the common scenario of adults who are already safely taking aspirin for primary prevention.

Professor McEvoy said: “Our findings of the benefit of aspirin in reducing heart disease or stroke without an excess risk of bleeding in some patients could be due to the fact that adults already taking aspirin without a prior bleeding problem are inherently lower risk for a future bleeding problem from the medication. Therefore, they seem to get more of the benefits of aspirin with less of the risks.

“These results are hypothesis-generating, but at present are the best available data. Until further evidence becomes available, it seems reasonable that persons already safely treated with low-dose aspirin for primary prevention may continue to do so, unless new risk factors for aspirin-related bleeding develop.”

Source: University of Galway

Categories : AgeingTags :

More Schooling is Linked to Slowed Aging and Increased Longevity

On By ModernMedia
Photo by Andrea Piacquadio on Pexels

Participants in the Framingham Heart Study who achieved higher levels of education tended to age more slowly and went on to live longer lives as compared to those who did not achieve upward educational mobility, according to a new study at Columbia University Mailman School of Public Health and The Robert N. Butler Columbia Aging Center. Upward educational mobility was significantly associated with a slower pace of aging and lower risk of death. The results are published online in JAMA Network Open.

The Framingham Heart Study is an ongoing observational study first initiated in 1948 that currently spans three generations.

The Columbia analysis is the first to connect educational mobility with pace of biological aging and mortality. “We’ve known for a long time that people who have higher levels of education tend to live longer lives. But there are a bunch of challenges in figuring out how that happens and, critically, whether interventions to promote educational attainment will contribute to healthy longevity,” said Daniel Belsky, PhD, associate professor of Epidemiology at Columbia Mailman School and the Aging Center and senior author of the paper.

To measure pace of aging, the researchers applied an algorithm known as the DunedinPACE epigenetic clock to genomic data collected by the Framingham Heart Study. The latest findings showed that, according to the yardstick of the DunedinPACE epigenetic clock, two years of additional schooling translated to a two- to three percent slower pace of aging. This slowing in the pace of aging corresponds to a roughly 10 percent reduction in risk of mortality in the Framingham Heart Study, according to previous research by Belsky on the association of DunedinPACE with risk of death.

DunedinPACE was developed by the Columbia researchers and colleagues and reported in January 2022. Based on an analysis of chemical tags on the DNA contained in white blood cells, or DNA methylation marks, DunedinPACE is named after the Dunedin Study birth cohort used to develop it. DunedinPACE (stands for Pace of Aging Computed from the Epigenome), is measured from a blood test and functions like a speedometer for the aging process, measuring how fast or slow a person’s body is changing as they grow older.

Biological aging refers to the accumulation of molecular changes that progressively undermine the integrity and resilience capacity of our cells, tissues and organs as we grow older.

The Columbia researchers used data from 14 106 Framingham Heart Study spanning three generations to link children’s educational attainment data with that of their parents. They then used data from a subset of participants who provided blood samples during data collection to calculate the pace of biological aging using the DunedinPACE epigenetic clock. In primary analysis, the researchers tested associations between educational mobility, aging, and mortality in a subset of 3101 participants for whom educational mobility and pace of aging measures could be calculated.

For 2437 participants with a sibling, the researchers also tested whether differences in educational attainment between siblings was associated with a difference in the pace of aging.

“A key confound in studies like these is that people with different levels of education tend to come from families with different educational backgrounds and different levels of other resources,” explained Gloria Graf, a PhD candidate in the Department of Epidemiology supervised by Belsky, and first author of the study. “To address these confounds, we focused on educational mobility, how much more (or less) education a person completed relative to their parents, and sibling differences in educational attainment – how much more (or less) education a person completed relative to their siblings. These study designs control for differences between families and allow us to isolate the effects of education.”

By combining these study designs with the new DunedinPACE epigenetic clock, the researchers were able to test how education affects the pace of aging. Then, by linking the education and pace of aging data with longitudinal records of how long participants lived, the team was able to determine if a slower pace of aging accounted for increased longevity in people with more education.

“Our findings support the hypothesis that interventions to promote educational attainment will slow the pace of biological aging and promote longevity,” noted Graf. “Ultimately, experimental evidence is needed to confirm our findings,” added Belsky. “Epigenetic clocks like DunedinPace have potential to enhance such experimental studies by providing an outcome that can reflect impacts of education on healthy aging well before the onset of disease and disability in later life.”

“We found that upward educational mobility was associated both with a slower pace of aging and decreased risk of death,” said Graf. “In fact, up to half of the educational gradient in mortality we observed was explained by healthier aging trajectories among better-educated participants.” This pattern of association was similar across generations and held within family sibling comparisons: siblings with higher educational mobility tended to have a slower pace of aging as compared with their less educated siblings.

Source: Columbia University’s Mailman School of Public Health

Categories : Diet and NutritionTags :

How the Body’s Organs Respond to Seven Days without Food

On By ModernMedia
Photo by jamie he: https://www.pexels.com/photo/round-gray-bowl-563067/

New findings reveal that the body undergoes significant, systematic changes across multiple organs during prolonged periods of fasting. The results published in Nature Metabolism, demonstrate evidence of health benefits beyond weight loss, but also show that any potentially health-altering changes appear to occur only after three days without food.

By identifying the potential health benefits from fasting and their underlying molecular basis, researchers from Queen Mary University of London’s Precision Healthcare University Research Institute (PHURI) and the Norwegian School of Sports Sciences provide a road map for future research that could lead to therapeutic interventions – including for people that may benefit from fasting but cannot undergo prolonged fasting or fasting-mimicking, such as ketogenic, diets.

Over millennia, humans have developed the ability to survive without food for prolonged periods of time. Fasting is practiced by millions of people throughout the world for different medical and cultural purposes, including health benefits and weight loss. Since ancient times, it has been used to treat diseases such as epilepsy and rheumatoid arthritis.

During fasting, the body changes its source and type of energy, switching from consumed calories to using its own fat stores. However, beyond this change in fuel sources, little is known about how the body responds to prolonged periods without food and any health impacts – beneficial or adverse – this may have. New techniques allowing researchers to measure thousands of proteins circulating in our blood provide the opportunity to systematically study molecular adaptions to fasting in humans in great detail.

Researchers followed 12 healthy volunteers taking part in a seven-day water-only fast. The volunteers were monitored closely on a daily basis to record changes in the levels of around 3000 proteins in their blood before, during, and after the fast. By identifying which proteins are involved in the body’s response, the researchers could then predict potential health outcomes of prolonged fasting by integrating genetic information from large-scale studies.

As expected, the researchers observed the body switching energy sources – from glucose to fat stored in the body – within the first two or three days of fasting. The volunteers lost an average of 5.7kg of both fat mass and lean mass. After three days of eating after fasting, the weight stayed off – the loss of lean was almost completely reversed, but the fat mass stayed off.

For the first time, the researchers observed the body undergoing distinct changes in protein levels after about three days of fasting – indicating a whole-body response to complete calorie restriction. Overall, one in three of the proteins measured changed significantly during fasting across all major organs. These changes were consistent across the volunteers, but there were signatures distinctive to fasting that went beyond weight loss, such as changes in proteins that make up the supportive structure for neurons in the brain.

Claudia Langenberg, Director of Queen Mary’s Precision Health University Research Institute (PHURI), said:

“For the first time, we’re able to see what’s happening on a molecular level across the body when we fast. Fasting, when done safely, is an effective weight loss intervention. Popular diets that incorporate fasting — such as intermittent fasting — claim to have health benefits beyond weight loss. Our results provide evidence for the health benefits of fasting beyond weight loss, but these were only visible after three days of total caloric restriction — later than we previously thought.”

Maik Pietzner, Health Data Chair of PHURI and co-lead of the Computational Medicine Group at Berlin Institute of Health at Charité, said:

“Our findings have provided a basis for some age-old knowledge as to why fasting is used for certain conditions. While fasting may be beneficial for treating some conditions, often times, fasting won’t be an option to patients suffering from ill health. We hope that these findings can provide information about why fasting is beneficial in certain cases, which can then be used to develop treatments that patients are able to do.”

Source: Queen Mary University of London

Categories : HIVTags :

SA Company Set to Manufacture HIV Prevention Ring

On By ModernMedia

By Catherine Tomlinson for Spotlight

Photo by Miguel Á. Padriñán: https://www.pexels.com/photo/syringe-and-pills-on-blue-background-3936368/

A company headquartered in Johannesburg will start making flexible silicone rings to protect women from HIV. The move signals a strong vote of confidence in an African firm to supply the ring at adequate scale and affordable prices, and a crucial step to making the continent self-reliant, reports Catherine Tomlinson.

A South African company has secured the rights to manufacture a vaginal ring used to prevent HIV infection. The ring, which is inserted and removed by the user, provides protection for a month, after which it has to be replaced with a new ring. The ring contains an antiretroviral drug called dapivirine.

While studies show that the dapivirine vaginal ring is less effective at preventing HIV than HIV prevention pills and injections, it has benefits over other tools that have led the World Health Organization (WHO) to recommend its inclusion in the package of sexual health services available to women.

One advantage of the ring over HIV prevention pills is that it can be used discreetly by women, allowing users to use the ring without having to negotiate or discuss its use and purpose with their sexual partners. This is particularly important in the context of South Africa where women face high rates of gender-based violence, which erodes their autonomy over their bodies and sexual and reproductive health.

“We need to give women more control over their health and bodies and access to a range of safe and effective options, including the dapivirine ring, to choose from so they can decide to use what works best for them at different times of their lives,” wrote several prominent women African activists in 2022.

Limited access

While the WHO recommended that the ring is offered to women, its current price is a barrier to broad use and rollout in South Africa. The only dapivirine vaginal ring approved by the South African Health Products Regulatory Authority that is currently available in the country is called the DapiRing.

The DapiRing is manufactured by a Swedish company, Sever Pharma Solutions, under a licence from the Population Council (formerly the International Partnership for Microbicides). It can be bought in South Africa’s private sector for R320, excluding dispensing fees.

The DapiRing is not available in South Africa’s public sector outside of study and pilot sites, as the National Essential Medicines List Committee, the body that determines which health technologies should be available in the country’s public health facilities, determined that the product is unaffordable at its current price. They estimate that the product will become affordable for South Africa’s public sector at a threshold price of R52 per ring.

Local company to boost access

The Population Council, the entity that owns the intellectual property on the dapivirine vaginal ring, selected South African pharmaceutical company Kiara Health to manufacture and supply the ring across Africa.

Kiara Health’s CEO, Dr Skhumbuzo Ngozwana, told Spotlight that while it is not yet known what the price of the Kiara manufactured ring will be, it is expected to be lower than the current price of the Swedish-manufactured DapiRing.

Licensc to manufacture

The council told Spotlight that the initial focus of the licence and partnership will be to develop manufacturing capacity at Kiara Health to supply the dapivirine vaginal ring across Africa. In the long term it is hoped that Kiara will be able to serve markets outside of Africa where there is a need for the ring.

The Population Council’s selection of an African-based manufacturing partner is notable as holders of intellectual property protections on HIV health technologies have typically sought out companies in Asia, and India in particular, as manufacturing partners.

Professor Linda-Gail Bekker, CEO of the Desmond Tutu HIV Foundation, told Spotlight: “If the “COVID-19 pandemic taught us anything, it is the value of being self-reliant as a region – being able to manufacture the vaginal ring is a step closer to Southern African self-reliance.”

Ngozwana said that Kiara Health appreciates that the Population Council have bucked the trend by not going to the East. “[A]ll these new technologies tend to go to the East, but instead they’ve partnered with an African company”.

Dapivirine vaginal ring. Credit: Columbia University Mailman School of Public Health

He added that future technology transfers to other manufacturers in Africa may be pursued if there is a need.

Exclusive supply licence

The Council told Spotlight that it intends to pursue an exclusive supply licence with Kiara Health for the sole supply of the dapivirine ring in Africa. The pursuit of an exclusive supply licence is a strong vote of confidence by the Population Council in the ability of Kiara Health to supply the ring at adequate scale and affordable prices.

Since Kiara Health’s exclusivity is for the supply of the ring, if there is a need, the company will be able to supply a dapivirine vaginal ring that is made by the Population Council’s Swedish manufacturing partner, Sever Pharma Solutions, that is already widely authorised for use in countries in Africa.

This would also guard against supply shortfalls that sometimes occur when only one manufacturer supplies a market, doctor Brid Devlin, the Population Council’s chief scientific officer, told Spotlight. “We would have two registered manufacturers right out the gate to guard against any shortfalls and have the opportunity to continue the supply as the demand grows.”

Why Kiara Health was chosen

Devlin added that the Population Council did not have a formal bid process through which Kiara Health was selected as the manufacturing partner for the ring, but rather that Kiara Health was selected following years of engagement with the company.

“We had a team that went to Kiara last year to see this site and it was a really impressive operation, both in terms of the staff but also the entire manufacturing operation,” she said.

Ngozwana told Spotlight that Kiara Health has existing manufacturing facilities in Johannesburg where capacity to produce the ring will be established.

Kiara Health’s manufacturing facilities already hold the quality assurance certifications (cGMP certification) required to manufacture medicines and have adequate space in Johannesburg to establish and scale manufacturing capacity for the ring, Ngozwana told Spotlight.

What is needed to manufacture the ring locally?

Critical steps include technology transfer, securing financing, procuring and importing manufacturing equipment, developing validation batches, and seeking regulatory approvals.

At this stage, there are still unknowns regarding the extent of data and testing that will be required to gain regulatory approval of Kiara Health’s dapivirine vaginal ring. To aid regulatory authorisation, Ngozwana and Devlin noted that Kiara Health would use the same manufacturing technology and inputs, including active pharmaceutical ingredients (API) used by Sever Pharma Solutions. This will require Kiara Health to import manufacturing equipment and API from Europe.

However, in the long term, Ngozwana said that Kiara Health would hope to increasingly procure manufacturing inputs, including potentially dapivirine API from the Pretoria-based API manufacturer CPT Pharma. (Spotlight previously reported on CPT Pharma’s work on API production here).

Ngozwana and Devlin told Spotlight that the anticipated time-limiting factors for establishing manufacturing capacity are securing financing and procuring and importing manufacturing equipment.

Funding has long been a challenge for African-based pharmaceutical companies since it has historically been scarce and only available on unfavourable terms. However, Ngozwana told Spotlight that Kiara Health is already engaging potential funders for support and exploring different financing sources, including grants and debt instruments.

Ngozwana and Devlin noted that technology transfer, which is a process for transferring manufacturing skills and knowledge, has already begun.

Can this license boost further domestic manufacturing capacity?

While vaginal rings are a relatively new type of health technology, they have multiple potential applications. A vaginal ring to prevent pregnancy has been available since the early 2000s and work is underway to develop a ring that is effective in combating both HIV and pregnancy. A dapivirine ring that reduces one’s risk of contracting HIV for three months – as opposed to one month – is also under development.

Kiara Health will seek to position itself to manufacture other vaginal rings entering the market, Ngozwana said. He added that in the long term, the company hoped that the partnership with the Population Council will be broadened to allow for local manufacturing of other sexual and reproductive health technologies in their product portfolio.

Republished from Spotlight under a Creative Commons licence.

Source: Spotlight