Month: March 2024

Categories : Obstetrics & GynaecologyTags :

New Study Links Placental Oxygen Levels to Foetal Brain Development

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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

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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

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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

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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

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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

Categories : Allergies PaediatricsTags :

Sublingual Immunotherapy for Food Allergies Safe and Effective for High-risk Children

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Photo by Corleto on Unsplash

New research from the University of British Columbia reveals a safe path to overcoming food allergies for older children and others who can’t risk consuming allergens orally to build up their resistance. Sublingual immunotherapy (SLIT) involves placing smaller amounts of food allergens under the tongue.

A study conducted by UBC clinical professor and paediatric allergist Dr Edmond Chan and his team at BC Children’s Hospital Research Institute found SLIT to be as safe and effective for high-risk older children and adolescents as oral immunotherapy is for preschoolers.

The study was published in The Journal of Allergy and Clinical Immunology.

“Our work confirms the safety and effectiveness of SLIT for older children and adolescents with multiple food allergies at higher risk of severe reaction,” said Dr Chan. “These are patients for whom oral immunotherapy would typically be denied because it’s felt to be too risky, so this could be the best approach for that population.”

Previously published research from Dr Chan’s team has shown that preschool oral immunotherapy is safe and effective in the real world. The protocol involves a “build-up phase” of several months, when patients visit a clinic every two weeks to ingest a higher dose of an allergen under medical supervision before continuing the same daily dose between visits. When they reach a certain dose – usually around 300mg of protein – they enter a “maintenance phase” during which they take that target daily dose at home. After a year of maintenance doses, approximately four out of five patients are able to pass an oral challenge test in which they tolerate a much higher dose of 4000mg of protein.

However, the build-up phase is risky for older children and those with a history of severe reactions. Dr Chan’s group has been looking for a safer way to get this at-risk group of patients to the maintenance phase.

They recruited about 180 such patients between the ages of four and 18, most with multiple food allergies. The SLIT protocol (started when COVID-19 pandemic restrictions were in place) required patients to have virtually supervised appointments 3-5 times over several months to build up to a small dose – in most cases, just 2mg of protein – which is absorbed through the membranes under the tongue rather than swallowed and ingested.

The patients’ caregivers learned how to mix and administer these doses at home using novel recipes based on products you can buy at the grocery store, developed with the team’s research dietitian. A wide variety of allergens were treated, including peanut, other legumes, tree nuts, sesame, other seeds, egg, cow’s milk, fish, wheat, shrimp, and other allergens. Patients took these doses daily for 1–2 years.

“It takes up to twice as long as oral immunotherapy, but we wouldn’t have had it any other way, because we needed the superior safety of SLIT for these older kids that are felt to be more severe,” said Dr. Chan.

While most patients had mild symptoms during the build-up phase, none had severe reactions during either build-up or maintenance. Seventy per cent of those tested at the end of the protocol could tolerate 300mg of their allergen – a success rate nearly as high as that for oral immunotherapy.

The results were encouraging for a therapy that any family can undertake at home with guidance from professionals.

“Besides safety considerations in older children, allergists are often quite burdened by the oral immunotherapy build-up phase, where a patient may require 11 or more visits to the clinic. They just don’t feel they have the capacity to offer that many visits in their office,” said Dr Chan. “In our clinic, we are starting to do more home-based approaches because the demand for medical appointments that would allow supervision far outstrips the supply. We are trying to develop an approach, based on data, that matches a patient’s risk level with the appropriate amount of supervision. Our SLIT data suggests that home-based SLIT build-up is safe.”

Ultimately, the trial highlights an alternative that allergists should now consider for patients who cannot safely undertake oral immunotherapy. The trade-off for greater safety is simply a longer timeline, but it comes with the benefit of keeping clinics free for those who need them most.

Source: University of British Columbia

Categories : Ageing ExerciseTags :

Yoga Provides Unique Cognitive Benefits to Older Women at Risk of Alzheimer’s disease

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Photo by Mikhail Nilov

A new UCLA Health study found Kundalini yoga provided several benefits to cognition and memory for older women at risk of developing Alzheimer’s disease including restoring neural pathways, preventing brain matter decline and reversing aging and inflammation-associated biomarkers – improvements not seen in a group who received standard memory training exercises.

The findings, published in the journal Translational Psychiatry, are the latest in a series of studies led by UCLA Health researchers over the past 15 years into the comparative effects of yoga and traditional memory enhancement training on slowing cognitive decline and addressing other risk factors of dementia.

Led by UCLA Health psychiatrist Dr. Helen Lavretsky of the Jane and Terry Semel Institute for Neuroscience and Human Behavior, this latest study sought to determine whether Kundalini yoga could be used early on to prevent cognitive decline and trajectories of Alzheimer’s disease among postmenopausal women.

Women have about twice the risk of developing Alzheimer’s disease compared to men due to several factors including longer life expectancy, changes in oestrogen levels during menopause and genetics.

In the new study, a group of more than 60 women ages 50 and older who had self-reported memory issues and cerebrovascular risk factors were recruited from a UCLA cardiology clinic. The women were divided evenly into two groups. The first group participated in weekly Kundalini yoga sessions for 12 weeks while the other one group underwent weekly memory enhancement training during the same time period. Participants were also provided daily homework assignments.

Kundalini yoga is a method that focuses on meditation and breath work more so than physical poses. Memory enhancement training developed by the UCLA Longevity centre includes a variety of exercises, such as using stories to remember items on a list or organising items on a grocery list, to help preserve or improve long-term memory of patients.

Researchers assessed the women’s cognition, subjective memory, depression and anxiety after the first 12 weeks and again 12 weeks later to determine how stable any improvements were. Blood samples were also taken to test for gene expression of aging markers and for molecules associated with inflammation, which are contributing factors to Alzheimer’s disease. A handful of patients were also assessed with MRIs to study changes in brain matter.

Researchers found the Kundalini yoga group participants saw several improvements not experienced by the memory enhancement training group. These included significant improvement in subjective memory complaints, prevention in brain matter declines, increased connectivity in the hippocampus which manages stress-related memories, and improvement in the peripheral cytokines and gene expression of anti-inflammatory and anti-aging molecules.

“That is what yoga is good for – to reduce stress, to improve brain health, subjective memory performance and reduce inflammation and improve neuroplasticity,” Lavretsky said.

Among the memory enhancement training group, the main improvements were found to be in the participants’ long-term memory.

Neither group saw changes in anxiety, depression, stress or resilience, though Lavretsky stated this is likely because the participants were relatively healthy and were not depressed.

While the long-term effects of Kundalini yoga on preventing or delaying Alzheimer’s disease require further study, Lavretsky said the study demonstrates that using yoga and memory training in tandem could provide more comprehensive benefits to the cognition of older women.

“Ideally, people should do both because they do train different parts of the brain and have different overall health effects,” Lavretsky said. “Yoga has this anti-inflammatory, stress-reducing, anti-aging neuroplastic brain effect which would be complementary to memory training.”

Source: University of California – Los Angeles Health Sciences

Categories : Cancer New Compounds and TreatmentsTags :

Dual Immunotherapy Drugs Show Promise vs a Range of Advanced Cancers

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Squamous cancer cell being attacked by cytotoxic T cells. Image by National Cancer Institute on Unsplash

In an early phase clinical trial, a combination of antibody-based medications targeting the immune system generated promising safety data and anti-tumour activity in individuals with various types of advanced cancer. The findings appear online in CANCER, a peer-reviewed journal of the American Cancer Society.

Both medications tested in the trial are checkpoint inhibitors, and support immune responses against tumour cells. CS1002 increases the activation and proliferation of T immune cells by binding to a T cell receptor called CTLA-4. CS1003, also called nofazinlimab, blocks the programmed cell death protein 1 that is expressed on various types of immune cells and plays a role in suppressing the immune system.

In this first-in-human multicentre, open-label study conducted from April 26, 2018 to January 18, 2022 at 9 study sites in Australia and China, phase Ia involved monotherapy dose-escalation (Part 1), which was followed by phase Ib combination therapy dose escalation (Part 2) and expansion (Part 3). Various dosing schedules of CS1002 (0.3, 1, or 3mg/kg once every three weeks, or 3mg/kg once every 9 weeks) were evaluated with 200mg CS1003 once every three weeks.

Parts 1, 2, and 3 of the trial included 13, 18, and 61 patients, respectively, who had advanced/metastatic solid, relapsed, or refractory tumors. During treatment, investigators did not observe any dose-limiting toxicities or a maximum tolerated dose. Treatment-related side effects such as diarrhoea, fatigue, and rash were reported in 30.8%, 83.3%, and 75.0% of patients in Parts 1, 2, and 3, respectively. Serious side effects such as intestinal inflammation and severe skin reactions were experienced by 15.4%, 50.0%, and 18.3% of patients in each part.

Of 61 patients evaluable for treatment efficacy, 23 (37.7%) with different types of tumours experienced a positive response. Higher response rates occurred with conventional and high-dose CS1002 regimens (1mg/kg once every three weeks or 3mg/kg once every 9 weeks) compared with low-dose CS1002 (0.3mg/kg once every three weeks) in certain cancers such as melanoma and skin cancer.

“CS1002 in combination with CS1003 had manageable safety profile across a broad dosing range and showed promising anti-tumor activities across CS1002 dose levels when combined with CS1003,” the investigators wrote. They concluded that this warranted more testing of CS1002 in combination with CS1003 for the treatment of solid tumours.

Source: Wiley

Categories : UrogenitalTags :

Prolonged Screentime Associated with Increased Nocturia

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Photo by Jan Antonin Kolar on Unsplash

In a study published in Neurourology and Urodynamics, adults who spent five or more hours a day watching TV and/or videos were more likely to develop nocturia, or the need to urinate multiple times during the night.

The study drew from 2011–2016 data from the National Health and Nutrition Examination Survey. Among 13 294 US individuals aged 20 and older, 4236 (31.86%) reported experiencing nocturia, while 9058 (68.14%) did not. Participants with five or more hours of TV and/or video viewing time per day had a 48% higher risk of experiencing nocturia compared with those with less than one hour of daily TV and/or video viewing time.

“As individuals increasingly engage in screen‐based activities, a comprehensive understanding of the impact of extended TV and/or video time on patterns of nocturia is crucial for both healthcare professionals and public health practitioners,” the authors wrote. “For individuals who engage in prolonged TV and/or video time, healthcare professionals can offer behavioural intervention recommendations, encouraging appropriate screen time management.”

Source: Wiley

Categories : Mental Health Obstetrics & GynaecologyTags :

Simple Cognitive-behavioural Intervention Reduces Postpartum Depression

On By ModernMedia
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Results from a large clinical trial published in Nature Medicine show that an intervention for anxiety provided to pregnant women living in Pakistan significantly reduced the likelihood of the women developing moderate-to-severe anxiety, depression, or both six weeks after birth. The unique intervention was administered by non-specialised providers who had the equivalent of a bachelor’s degree in psychology – but no clinical experience. The results suggest this intervention could be an effective way to prevent the development of postpartum mental health challenges in women living in low-resource settings.

“In low resource settings, it can be challenging for women to access mental health care due to a global shortage of trained mental health specialists,” said Joshua A. Gordon, MD, PhD, Director of the National Institute of Mental Health, part of the National Institutes of Health.

“This study shows that non-specialists could help to fill this gap, providing care to more women during this critical period.”

Led by Pamela J. Surkan, PhD, ScD, of Johns Hopkins Bloomberg School of Public Health, Baltimore, the study was conducted in the Punjab Province of Pakistan between April 2019 and January 2022.

Pregnant women with symptoms of at least mild anxiety were randomly assigned to receive either routine pregnancy care or a cognitive behavioral therapy (CBT)-based intervention called Happy Mother-Healthy Baby. The researchers assessed the participants (380 women in the CBT group and 375 women in the routine care group) for anxiety and depression six weeks after the birth of their child.

The researchers found that 9% of women in the intervention group developed moderate-to-severe anxiety compared with 27% of women in the routine care group.

Additionally, 12% percent of women in the intervention group developed depression compared with 41% of women in the routine care group.

“Postpartum depression not only harms mothers, it is also associated with poorer physical growth and delayed cognitive development in their children,” said Dr Surkan.

“The link between maternal and child health highlights the critical importance of developing effective ways to address postpartum anxiety and depression.”

The Happy Mother-Healthy Baby intervention was created using input from pregnant women in a hospital in Rawalpindi, Pakistan.

Pregnant women took part in six intervention sessions where they learned to identify anxious thoughts and behaviors, such as thoughts about possible miscarriage, and to practice replacing them with helpful thoughts and behaviors.

The first five sessions were conducted in early to mid-pregnancy, and the sixth session occurred in the third trimester.

Prior research suggests that up to 30% of women in the Global South, which includes South America, Africa, and most of southern Asia, report experiencing anxiety during pregnancy.

Anxiety during pregnancy predicts the development of anxiety and depression after birth, making the prenatal period a prime target for intervention.

However, it can be challenging for women living in low-resource settings to access trained clinical care.

The findings from this study demonstrate that an intervention such as Happy Mother-Healthy Baby could be an effective way to help prevent the development of postpartum depression and anxiety in settings where specialist clinical care may be hard to access.

“In the future, we can build on these findings through implementation research. Having identified an intervention that works, the next step is to figure out the best ways to deliver effective treatment to the people who need it, bridging the gap between science and practice,” said Dr Surkan.

Source: NIH/National Institute of Mental Health