Month: August 2024

Sugar Intake Decreasing but Still Too High

Further action needed, according to a University of Bonn study on child and adolescent nutrition

Photo by Patrick Fore on Unsplash

University of Bonn researchers have analysed data on sugar intake among children and adolescents in a long-term study, finding that intake has been declining steadily since 2010 – but is still above the level recommended by the World Health Organization (WHO). The results, to be published in the European Journal of Nutrition, are already available online.

“Our study concerns the intake of free sugars,” explains Dr Ines Perrar, who is a research associate at the University of Bonn Institute of Nutritional and Food Science (IEL) and lead author of the study. “There is debate on whether sugar, like salt and fats, is linked to the development of chronic diseases.” The WHO defines “free” sugar as any form of sugar, including honey, syrup and fruit juice concentrates, added by a manufacturer or when preparing food and beverages at home. Free sugar also includes sugar naturally occurring in juices.

For their project, IEL researchers analysed data from the “Dortmund Nutritional and Anthropometric Longitudinally Designed” cohort study (DONALD). The DONALD study has been ongoing since 1985, gathering detailed data on nutrition, metabolism, growth and health of children and adolescents. “Study participants weigh and document everything they eat and drink on three consecutive days every year,” relates Dr Ute Nöthlings, Professor of Nutritional Epidemiology at the IEL. “Referring to our Institute’s in-house nutrient database, we are able to estimate intake of certain nutrients, including free sugars.”

Sugar intake too high among adolescents in particular

The authors evaluated 4218 sets of three-day weighing dietary records by 751 children and adolescents between ages three and 18 in the years 2010–2023. “Our finding is that free sugar intake continues to decline,” Dr Perrar notes, “but average daily intake still exceeds the level recommended by the WHO and the German Nutrition Society (Deutsche Gesellschaft für Ernährung, DGE) of a maximum 10% of total daily energy intake.”

An analysis of DONALD back in 2019 already indicated that free sugar intake has been declining since 2005, then in 2016 a median value of approximately 16% of daily energy intake was determined. That value has subsequently declined further to 11.7%. The researchers surmise this trend may be explained by increased awareness of the health consequences of excessive consumption of sugar-sweetened beverages and certain other sugary foods.

While the decline definitely represents good progress, there are noteworthy age group differences, as Professor Nöthlings points out, who is director of the DONALD study, spokesperson for the Transdisciplinary Research Area (TRA) Sustainable Futures and a member of the Life and Health TRA at the University of Bonn: “During the observation period, we saw a relatively high intake of free sugars around 15 percent of the daily energy intake in some cases, particularly among adolescents aged six to 14. The intake then declines significantly with increasing age.”

Actual sugar intake likely higher

The researchers point out that the actual sugar intake is likely higher than the study data suggests, due in part to potential under-reporting by the study participants self-reporting on what they eat. In addition, the study is not broadly representative of society, as the design of this large study favours participation by families of a rather higher socioeconomic status who are generally more aware regarding nutrition and health issues.

Source: University of Bonn

Shingles Increases Risk of Cognitive Decline in Later Life

The risk was higher for men who were carriers of a gene linked to dementia

Photo by Mari Lezhava on Unsplash

A new study led by investigators from Brigham and Women’s Hospital found that an episode of shingles is associated with about a 20 percent higher long-term risk of subjective cognitive decline. The study’s findings provide additional support for getting the shingles vaccine to decrease risk of developing shingles, according to the researchers. Their results are published in Alzheimer’s Research & Therapy.

“Our findings show long-term implications of shingles and highlight the importance of public health efforts to prevent and promote uptake of the shingles vaccine,” said corresponding author Sharon Curhan, MD, of the Channing Division for Network Medicine at Brigham and Women’s Hospital. “Given the growing number of Americans at risk for this painful and often disabling disease and the availability of a very effective vaccine, shingles vaccination could provide a valuable opportunity to reduce the burden of shingles and possibly reduce the burden of subsequent cognitive decline.”

Shingles, medically known as “herpes zoster,” is a viral infection that often causes a painful rash. Shingles is caused by the varicella zoster virus (VZV), the same virus that causes chickenpox. After a person has chickenpox, the virus stays in their body for the rest of their life. Most of the time, our immune system keeps the virus at bay. Years and even decades later, the virus may reactivate as shingles.

Almost all individuals in the US age 50 years and older have been infected with VZV and are therefore at risk for shingles. There’s a growing body of evidence that herpes viruses, including VZV, can influence cognitive decline. Subjective cognitive decline is an individual’s self-perceived experience of worsening or more frequent confusion or memory loss. It is a form of cognitive impairment and is one of the earliest noticeable symptoms of Alzheimer’s disease and related dementias.

Previous studies of shingles and dementia have been conflicting. Some research indicates that shingles increases the risk of dementia, while others indicate there’s no association or a negative association. In recent studies, the shingles vaccine was associated with a reduced risk of dementia.

To learn more about the link between shingles and cognitive decline, Curhan and her team used data from three large, well-characterized studies of men and women over long periods: The Nurses’ Health Study, the Nurses’ Health Study 2, and the Health Professionals Follow-Up Study. The study included 149,327 participants who completed health status surveys every two years, including questions about shingles episodes and cognitive decline. They compared those who had shingles with those who didn’t.

Curhan designed the study with first author Tian-Shin Yeh, formerly of the Harvard TH Chan School of Public Health. The researchers found that a history of shingles was significantly and independently associated with a higher risk – approximately 20% higher – of subjective cognitive decline in both women and men. That risk was higher among men who were carriers of the gene APOE4, which is linked to cognitive impairment and dementia. That same association wasn’t present in the women.

Researchers don’t know the mechanisms that link the virus to cognitive health, but there are several possible ways it may contribute to cognitive decline. There is growing evidence linking VZV to vascular disease, called VZV vasculopathy, in which the virus causes damage to blood vessels in the brain or body. Curhan’s group previously found that shingles was associated with higher long-term risk of stroke or heart disease.

Other mechanisms that may explain how the virus may lead to cognitive decline include causing inflammation in the brain, directly damaging the nerve and brain cells, and the activation of other herpesviruses.

The limitations of this research include that it was an observational study, information was based on self-report, and included a mostly white, highly educated population. In future studies, the researchers hope to learn more about preventing shingles and its complications.

“We’re evaluating to see if we can identify risk factors that could be modified to help reduce people’s risk of developing shingles,” Curhan said. “We also want to study whether the shingles vaccine can help reduce the risk of adverse health outcomes from shingles, such as cardiovascular disease and cognitive decline.” 

Source: Brigham and Women’s Hospital

WHO Declares International Public Health Emergency over Mpox Outbreak

Mpox (monkeypox) virus. Source: NIH

WHO Director-General Dr Tedros Adhanom Ghebreyesus has determined that the upsurge of mpox in the Democratic Republic of the Congo (DRC) and a growing number of countries in Africa constitutes a public health emergency of international concern (PHEIC) under the International Health Regulations (2005) (IHR).

Dr Tedros’s declaration came on the advice of an IHR Emergency Committee of independent experts who met earlier in the day to review data presented by experts from WHO and affected countries. The Committee informed the Director-General that it considers the upsurge of mpox to be a PHEIC, with potential to spread further across countries in Africa and possibly outside the continent.

The Director-General will share the report of the Committee’s meeting and, based on the advice of the Committee, issue temporary recommendations to countries.

In declaring the PHEIC, Dr Tedros said, “The emergence of a new clade of mpox, its rapid spread in eastern DRC, and the reporting of cases in several neighbouring countries are very worrying. On top of outbreaks of other mpox clades in DRC and other countries in Africa, it’s clear that a coordinated international response is needed to stop these outbreaks and save lives.”

WHO Regional Director for Africa Dr Matshidiso Moeti said, “Significant efforts are already underway in close collaboration with communities and governments, with our country teams working on the frontlines to help reinforce measures to curb mpox. With the growing spread of the virus, we’re scaling up further through coordinated international action to support countries bring the outbreaks to an end.”

Committee Chair Professor Dimie Ogoina said, “The current upsurge of mpox in parts of Africa, along with the spread of a new sexually transmissible strain of the monkeypox virus, is an emergency, not only for Africa, but for the entire globe. Mpox, originating in Africa, was neglected there, and later caused a global outbreak in 2022. It is time to act decisively to prevent history from repeating itself.”

This PHEIC determination is the second in two years relating to mpox. Caused by an Orthopoxvirus, mpox was first detected in humans in 1970, in the DRC. The disease is considered endemic to countries in central and west Africa.

In July 2022, the multi-country outbreak of mpox was declared a PHEIC as it spread rapidly via sexual contact across a range of countries where the virus had not been seen before. That PHEIC was declared over in May 2023 after there had been a sustained decline in global cases.

Mpox has been reported in the DRC for more than a decade, and the number of cases reported each year has increased steadily over that period. Last year, reported cases increased significantly, and already the number of cases reported so far this year has exceeded last year’s total, with more than 15 600 cases and 537 deaths.

The emergence last year and rapid spread of a new virus strain in DRC, clade 1b, which appears to be spreading mainly through sexual networks, and its detection in countries neighbouring the DRC is especially concerning, and one of the main reasons for the declaration of the PHEIC.

In the past month, over 100 laboratory-confirmed cases of clade 1b have been reported in four countries neighbouring the DRC that have not reported mpox before: Burundi, Kenya, Rwanda and Uganda. Experts believe the true number of cases to be higher as a large proportion of clinically compatible cases have not been tested.

Several outbreaks of different clades of mpox have occurred in different countries, with different modes of transmission and different levels of risk.

The two vaccines currently in use for mpox are recommended by WHO’s Strategic Advisory Group of Experts on Immunization, and are also approved by WHO-listed national regulatory authorities, as well as by individual countries including Nigeria and the DRC.

Last week, the Director-General triggered the process for Emergency Use Listing for mpox vaccines, which will accelerate vaccine access for lower-income countries which have not yet issued their own national regulatory approval. Emergency Use Listing also enables partners including Gavi and UNICEF to procure vaccines for distribution.

WHO is working with countries and vaccine manufacturers on potential vaccine donations, and coordinating with partners through the interim Medical Countermeasures Network to facilitate equitable access to vaccines, therapeutics, diagnostics and other tools.

WHO anticipates an immediate funding requirement of an initial US$ 15 million to support surveillance, preparedness and response activities. A needs assessment is being undertaken across the three levels of the Organization.

To allow for an immediate scale up, WHO has released US$ 1.45 million from the WHO Contingency Fund for Emergencies and may need to release more in the coming days. The Organization appeals to donors to fund the full extent of needs of the mpox response.

Source: WHO

From Bottlenecks to Breakthroughs: BHF Report Charts the Course for Southern Africa’s Healthcare Future

Photo by Hush Naidoo on Unsplash

By adopting bold, transformative strategies, the healthcare industry can overcome critical challenges and foster innovative collaborations to create a more equitable and sustainable healthcare future for southern Africa, writes Dr Katlego Mothudi, Managing Director at the Board of Healthcare Funders (BHF).

Committed to promoting collaboration and creating actionable insights within southern Africa’s healthcare ecosystem, BHF’s recently published report highlights significant trends, obstacles and breakthrough solutions from key figures in the healthcare sector, and charts the course for a robust, inclusive healthcare future. 

By interviewing industry leaders – including funders, hospitals, clinicians, and the pharmaceutical sector – the report presents a strategic path forward that promises to revolutionise the region’s healthcare landscape. As southern Africa grapples with rising healthcare costs, a growing burden of non-communicable diseases (NCDs), and economic instability, this report charts the course for a robust, inclusive healthcare future.

The evolving landscape of southern African healthcare

Healthcare organisations in southern Africa are navigating a complex landscape filled with escalating challenges and promising opportunities. The rapid increase in the burden of non-communicable diseases (NCDs) and economic volatility is driving a critical shift toward more sustainable healthcare models while increasing healthcare costs and reducing affordability. 

Concurrently, there is a renewed commitment to achieving health equity, with concerted efforts to ensure healthcare is universally accessible. Universal Health Coverage (UHC) is in various stages of rollout across the region, reflecting varying national priorities and capabilities. In South Africa, the proposed National Health Insurance (NHI), despite its controversies, is being closely watched for its potential impact on other countries if implemented pragmatically.

In the private sector, the health insurance market shows notable growth. This is in contrast to stagnation relating to traditional medical schemes. These schemes face slow or no membership growth and rising utilisation rates, pushing a gradual shift towards value-based care with strategies to strengthen contracting arrangements, control expenditure and improve health outcomes. 

High levels of fraud, waste and abuse persist, particularly in southern Africa, where economic conditions have severely limited the growth of private health insurance or medical scheme coverage, highlighting the critical need for innovative healthcare financing solutions.

Additionally, the post-COVID acceleration of digital healthcare is gradually reshaping service delivery. Significant investments in artificial intelligence and predictive analytics are set to strengthen health risk management, boost patient care and enhance operational efficiency. 

This era of digital transformation is marked by collaborations with local and global tech innovators and a strategic internal focus on tech integration to overhaul legacy systems and traditional practices. This complex tapestry of trends indicates a critical juncture for the region’s healthcare, laden with challenges, yet rich with opportunities for pioneering change.

Bottlenecks and barriers

Southern Africa’s healthcare systems face significant barriers to sustainability, including inefficient and politicised regulatory environments, inadequate workforce training, economic instability and the growing corporatisation of healthcare, all of which hinder innovation, affordability and access while threatening both public trust and the quality of care.

Reactive responses to emerging challenges

In response to the bottlenecks and challenges facing the sector, healthcare organisations across southern Africa are collaborating with government and business coalitions, such as Business for South Africa, to address fiscal risks and policy uncertainties, and promote private sector participation, regulatory harmonisation and advanced technologies. 

They are prioritising integrated healthcare models focused on primary care and value-based approaches, investing in digital innovations such as telemedicine, electronic health records and AI to improve efficiency and outcomes. Efforts to optimise resource allocation and care quality through digitalisation and process reengineering are also underway. 

While these actions address immediate challenges, longer-term systemic solutions are necessary to achieve UHC and future-proof their markets.

Proactive systemic responses

To create a sustainable and equitable healthcare environment in southern Africa, long-term strategic solutions are essential, and aimed at broadening healthcare access, enhancing system efficiency and ensuring financial sustainability. 

To achieve UHC, access through a multi-payer system that guarantees quality, affordable healthcare for all is instrumental. Implementing UHC principles will promote preventative care, care coordination, and effective management of chronic diseases. Additionally, advancing public-private partnerships (PPPs) can significantly enhance access and care quality, with proactive private sector engagement helping to overcome existing barriers and drive progress.

To improve policy and regulation, it is crucial to enhance the oversight and effectiveness of regulatory institutions while fostering regional inclusivity across the Southern African Development Community (SADC) for better knowledge sharing. 

In South Africa, aligning the NHI with a multi-funder framework will integrate private funders and recognise employers’ roles in system sustainability. Updating benefits to reflect current health needs and economic conditions will make healthcare more affordable and less hospital-centric. Introducing Low-Cost Benefit Options (LCBOs) within medical schemes will broaden access, while strengthening competition and optimising private sector performance, will enhance care quality. Additionally, establishing a risk equalisation fund and mandating medical scheme membership is key to stabilising the insurance market and lowering costs.

To advance healthcare, investments in infrastructure and technology are essential, especially in underserved areas, to ensure equitable access. Strengthening healthcare training and updating practice guidelines will improve care quality and expand capabilities, while better workforce planning and collaboration between academia and healthcare providers will align training with industry needs. Additionally, leveraging digital health initiatives, such as telemedicine and electronic health records, will enhance service reach and efficiency.

Furthermore, incorporating Environmental, Social, and Governance (ESG) principles is crucial for promoting resilience and establishing southern African healthcare systems as leaders in sustainable practices. Adopting ESG standards will enhance the sustainability and governance of these healthcare systems.

These strategies are designed not only to address immediate healthcare challenges, but also to establish a robust foundation for a future where high quality healthcare is universally accessible in southern Africa. By implementing these solutions, the region can bridge the current gaps and pave the way for a resilient healthcare system.

Through collaborative efforts, strategic reforms, and innovative solutions, southern Africa’s healthcare sector is not only meeting current needs but also preparing for future demands that are defined by innovation, equity and sustainability. 

Sanofi Commits to Affordable Insulin Pens for Diabetic Patients

Novolog insulin pen. Photo by Dennis Klicker on Unsplash

Over the past few years, there has been a notable shift towards the use of insulin pens in the public sector, replacing traditional vials. This transition has been driven by the advantages insulin pens offer, including improved dosing accuracy, ease of use for patients, greater convenience, and better adherence to treatment.1

The move to basal insulin is in line with the National Strategic Plan for the Prevention and Control of Non-Communicable Diseases 2022-2027, which outlines specific targets for managing diabetes. This plan aims to improve early detection and treatment of diabetes by ensuring that 90% of people over 18 know their blood pressure and blood sugar levels. It also aims for 60% of those with high levels to receive treatment, and 50% of those treated to have their levels under control. These measures are designed to improve the management and outcomes of diabetes in the population.2

Since May 2023, the Department of Health has faced insulin pen rationing as the previous sole supplier opted not to tender. Nearly 50% of the insulin required for patients was expected to come in pen sets. To mitigate the impact, the health department has sourced a limited supply of insulin pens and analogues for vulnerable groups like the elderly, young children, and visually impaired individuals, despite the higher cost of insulin analogues, which offer more convenient and effective blood sugar management.3

In 2021, long-acting analogue insulins were added to the WHO Model List of Essential Medicines (EML) and have significantly reduced aligning with those of human insulin.3 Recognising this need, Sanofi has adjusted the price of its basal insulin to the cost of human insulin in South Africa.

Sanofi has been engaging with the National Department of Health to meet the needs of vulnerable patient groups,” says Dr Asafika Mbangata, Medical Advisor for Diabetes and Established Products, Sanofi. “A circular has been released by the department, identifying patient groups that would benefit from analogue insulins. This includes vulnerable groups like the elderly, young children, and visually impaired individuals. Sanofi is committed to ensuring that patients have access to treatment which will help control the disease by achieving adequate glycaemic control and eventually, prevention of complications in South Africa.”

Long-acting insulin analogues offer significant clinical benefits over human insulin, including prolonged duration of action,4 more stable glucose control with less hypoglycaemia, and reduced need for multiple daily doses.5 These benefits are particularly crucial for patients experiencing dangerously low blood glucose levels with human insulin.5 In addition, reductions in HbA1c (a key blood sugar indicator) are greater with all basal insulin analogues compared to human basal insulins.6

Diabetes Type 1

It’s estimated that more than 31 000 people in South Africa live with Type 1 diabetes and require full insulin replacement therapy, with multiple daily injections. Among them, 5000 are children.7

“Insulin pens, which are more accurate, user-friendly, and associated with less pain when used with short and fine needles, significantly enhance their quality of life,” says Dr. Mbangata. “This is particularly important for children, who are more likely to adhere to their treatment schedules with the easier-to-use and less painful pens.”

Diabetes Type 2

According to the International Diabetes Federation (IDF), 4.2 million South African adults are living with diabetes, primarily type 2.7 Of these, 84% access diabetes care in the public sector. Diabetes is the second leading cause of death in South Africa, following tuberculosis, and the leading cause of death among females.8

More than 9% of the South African population is 60 or older.9 Around 600 000 elderly individuals are living with diabetes, with approximately 500 000 of them accessing public sector healthcare.10

Treating diabetes in the elderly often requires a multidrug regimen, including insulin therapy. However, due to comorbidities such as dementia, vision loss, neuropathies, poor mobility, and manual dexterity issues, elderly patients are at increased risk of hypoglycaemia and dosing errors associated with insulin administration. Insulin pen devices have been shown to provide more reliable, accurate, and simplified dosing, making them a safer and more acceptable method of insulin delivery for the elderly population.11

Impaired vision

Diabetic retinopathy (impaired vision) is the third most common cause of blindness in South Africa, following cataracts and glaucoma​​.12 A pilot project screening for diabetic retinopathy in primary care at three Cape Town community healthcare centres assessed 400 patients living with diabetes. Over 80% had significantly reduced visual acuity, and 63% had retinopathy.12 These visually impaired patients would greatly benefit from using insulin pens, which make a clicking sound when the dial is turned, indicating the dose.

“Against the backdrop of these statistics, Sanofi continues in its efforts to make insulin pens more affordable and accessible, and our aim is to improve the quality of life and healthcare outcomes for South Africa’s diabetic population,” says Prudence Selani, External Affairs Head, Sanofi.

References

  1. Diabetes Spectr 2012;25(2):117–122
  2. Health Policy Watch. New WHO Essential Medicines List Includes Controversial Insulin Analogues. Available from: https://healthpolicy-watch.news/who-essential-medicines-insulin-analogues/
  3. Brunetti VC et al. Diabetes ObesMetab. 2022;1–13
  4. Sims EK et al. Nat Med. 2021;27:1154-64
  5. MannucciE et al. Endocrine. 2021;74:508-17
  6. IDF Diabetes Atlas 10th edition 2021
  7. Report-03-08-012018 (www.statssa.gov.za)
  8. StatsSA report: Marginalised Groups Series VI: The Social Profile of Older Persons, 2017–2021
  9. Werfalli M, Kassanjee R, Kalula S, Kowal P, Phaswana-Mafuya N, Levitt NS. Diabetes in South African older adults: prevalence and impact on quality of life and functional disability – as assessed using SAGE Wave 1 data. Glob Health Action. 2018;11(1):1449924. doi: 10.1080/16549716.2018.1449924. PMID: 29699475; PMCID: PMC5933282.
  10. Wright BM, Bellone JM, McCoy EK. A review of insulin pen devices and use in the elderly diabetic population. Clin Med Insights Endocrinol Diabetes. 2010;3:53-63. doi: 10.4137/CMED.S5534. Epub 2010 Nov 22. PMID: 22879787; PMCID: PMC3411523.
  11. Bertram MY, Jaswal AV, Van Wyk VP, Levitt NS, Hofman KJ. The non-fatal disease burden caused by type 2 diabetes in South Africa, 2009. Glob Health Action 2013;6:12944. [http://dx.doi.org/10.3402/gha.v6i0.19244]
  12. Cairncross JP, Steinberg WJ, Labuschagne MJ. Prevalence of eye pathology in a group of diabetic patients at National District Hospital Outpatient Department in Bloemfontein, South Africa. Afr J Prim Health Care Fam Med. 2017 Sep 27;9(1):e1-e7. doi: 10.4102/phcfm.v9i1.1440. PMID: 29041796; PMCID: PMC5645559.

The Ageing Process Makes Big Jumps in Our 40s and 60s

Photo by LOGAN WEAVER | @LGNWVR on Unsplash

If it’s ever felt like everything in your body is breaking down at once, that might not be your imagination. A new Stanford Medicine study shows that many of our molecules and microorganisms dramatically rise or fall in number during our 40s and 60s.

Researchers assessed many thousands of different molecules in people from age 25 to 75, as well as their microbiomes – the bacteria, viruses and fungi that live inside us and on our skin – and found that the abundance of most molecules and microbes do not shift in a gradual, chronological fashion. Rather, we undergo two periods of rapid change during our life span, averaging around age 44 and age 60. A paper describing these findings was published in the journal Nature Aging.

“We’re not just changing gradually over time; there are some really dramatic changes,” said Michael Snyder, PhD, professor of genetics and the study’s senior author. “It turns out the mid-40s is a time of dramatic change, as is the early 60s. And that’s true no matter what class of molecules you look at.”

Xiaotao Shen, PhD, a former Stanford Medicine postdoctoral scholar, was the first author of the study. Shen is now an assistant professor at Nanyang Technological University Singapore.

These big changes likely impact our health – the number of molecules related to cardiovascular disease showed significant changes at both time points, and those related to immune function changed in people in their early 60s.

Abrupt changes in number

Snyder, the Stanford W. Ascherman, MD, FACS Professor in Genetics, and his colleagues were inspired to look at the rate of molecular and microbial shifts by the observation that the risk of developing many age-linked diseases does not rise incrementally along with years. For example, risks for Alzheimer’s disease and cardiovascular disease rise sharply in older age, compared with a gradual increase in risk for those under 60.

The researchers used data from 108 people they’ve been following to better understand the biology of aging. Past insights from this same group of study volunteers include the discovery of four distinct “ageotypes,” showing that people’s kidneys, livers, metabolism and immune system age at different rates in different people.

The new study analysed participants who donated blood and other biological samples every few months over the span of several years; the scientists tracked many different kinds of molecules in these samples, including RNA, proteins and metabolites, as well as shifts in the participants’ microbiomes. The researchers tracked age-related changes in more than 135 000 different molecules and microbes, for a total of nearly 250 billion distinct data points.

They found that thousands of molecules and microbes undergo shifts in their abundance, either increasing or decreasing – around 81% of all the molecules they studied showed non-linear fluctuations in number, meaning that they changed more at certain ages than other times. When they looked for clusters of molecules with the largest changes in amount, they found these transformations occurred the most in two time periods: when people were in their mid-40s, and when they were in their early 60s.

Although much research has focused on how different molecules increase or decrease as we age and how biological age may differ from chronological age, very few have looked at the rate of biological aging. That so many dramatic changes happen in the early 60s is perhaps not surprising, Snyder said, as many age-related disease risks and other age-related phenomena are known to increase at that point in life.

The large cluster of changes in the mid-40s was somewhat surprising to the scientists. At first, they assumed that menopause or perimenopause was driving large changes in the women in their study, skewing the whole group. But when they broke out the study group by sex, they found the shift was happening in men in their mid-40s, too.

“This suggests that while menopause or perimenopause may contribute to the changes observed in women in their mid-40s, there are likely other, more significant factors influencing these changes in both men and women. Identifying and studying these factors should be a priority for future research,” Shen said.

Changes may influence health and disease risk

In people in their 40s, significant changes were seen in the number of molecules related to alcohol, caffeine and lipid metabolism; cardiovascular disease; and skin and muscle. In those in their 60s, changes were related to carbohydrate and caffeine metabolism, immune regulation, kidney function, cardiovascular disease, and skin and muscle.

It’s possible some of these changes could be tied to lifestyle or behavioural factors that cluster at these age groups, rather than being driven by biological factors, Snyder said. For example, dysfunction in alcohol metabolism could result from an uptick in alcohol consumption in people’s mid-40s, often a stressful period of life.

The team plans to explore the drivers of these clusters of change. But whatever their causes, the existence of these clusters points to the need for people to pay attention to their health, especially in their 40s and 60s, the researchers said. That could look like increasing exercise to protect your heart and maintain muscle mass at both ages or decreasing alcohol consumption in your 40s as your ability to metabolise alcohol slows.

“I’m a big believer that we should try to adjust our lifestyles while we’re still healthy,” Snyder said.

Source: Stanford Medicine

New, Inexpensive Medical Computers that Run on Air

Closeup of the pneumatic logic sensing device. (William Grover/UCR)

Medical engineers have developed a new, air-powered computer sets off alarms when certain medical devices fail. The invention is a more reliable and lower-cost way to help prevent blood clots and strokes – all without electronic sensors. 

Described in a paper in the journal Device, the computer not only runs on air, but also uses air to issue warnings. It immediately blows a whistle when it detects a problem with the lifesaving compression machine it is designed to monitor.

Intermittent pneumatic compression (IPC) devices are pneumatic leg sleeves that periodically squeeze a patient’s legs to increase blood flow. This prevents clots that lead to blocked blood vessels, strokes, or death. Typically, these machines are powered and monitored by electronics.

“IPC devices can save lives, but all the electronics in them make them expensive. So, we wanted to develop a pneumatic device that gets rid of some of the electronics, to make these devices cheaper and safer,” said William Grover, associate professor of bioengineering at UC Riverside and corresponding paper author.

Pneumatics move compressed air from place to place. Emergency brakes on freight trains operate this way, as do bicycle pumps, tire pressure gauges, respirators, and IPC devices. It made sense to Grover and his colleagues to use one pneumatic logic device to control another and make it safer.

This type of device operates in a similar way to electronic circuits, by making parity bit calculations. “Let’s say I want to send a message in ones and zeroes, like 1-0-1, three bits,” Grover said. “Decades ago, people realized they could send these three bits with one additional piece of information to make sure the recipient got the right message.” 

That extra piece of information is called a parity bit. The bit is a number – 1 if the message contains an odd number of ones, and 0 if the message contains an even number of ones. Should the number one appear at the end of a message with an even number of bits, then it is clear the message was flawed. Many electronic computers send messages this way. 

An air-powered computer uses differences in air pressure flowing through 21 tiny valves to count the number of ones and zeroes. If no error in counting has occurred, then the whistle doesn’t blow. 

If it does blow, that’s a sign the machine requires repairs. Grover and his students, in a video demonstrating the air computer, are shown damaging an IPC device with a knife, rendering it unusable. Seconds later, the whistle blows.

“This device is about the size of a box of matches. It replaces a handful of sensors as well as a computer,” Grover said. “So, we can reduce costs while still detecting problems in a device. And it could also be used in high humidity or high temperature environments that aren’t ideal for electronics.”

The IPC device monitoring is only one application for air computing. For his next project, Grover would like to design a device that could eliminate the need for a job that kills people every year: moving around grain at the top of tall silos. 

Tall buildings full of corn or wheat, grain silos are a common sight in the Midwest. Often times, a human has to go inside with a shovel to break up the grains and even out the piles inside. 

“A remarkable number of deaths occur because the grain shifts and the person gets trapped. A robot could do this job instead of a person. However, these silos are explosive, and a single electric spark could blow a silo apart, so an electronic robot may not be the best choice,” Grover said. “I want to make an air-powered robot that could work in this explosive environment, not generate any sparks, and take humans out of danger.” 

Air-powered computing is an idea that has been around for at least a century. People used to make air-powered pianos that could play music from punched rolls of paper. After the rise of modern computing, engineers lost interest in pneumatic circuits.

“Once a new technology becomes dominant, we lose awareness of other solutions to problems,” Grover said. “One thing I like about this research is that it can show the world that there are situations today when 100-plus-year-old ideas can still be useful.”

Source: University of California Riverside

Less Sleep and Later Bedtime in Childhood Linked to Future Substance Use

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A good night’s sleep is essential for children’s health and development, but childhood sleep patterns may also be linked to future substance use. A new study, led by a team of Penn State researchers, found that adolescents were more likely to have consumed alcohol or tried marijuana by age 15 if they went to bed later and slept fewer hours during childhood and adolescence. The team published their findings in Annals of Epidemiology.

“The study suggests that there might be some critical ages when sleep can be a target for intervention,” said Anne-Marie Chang, associate professor of biobehavioural health at Penn State and senior author of the paper. “If we improve sleep in the school-age population, not only could that show improvements in sleep health but in other aspects like the decision to engage in risky behaviours like alcohol and other substance use.”

The research team explored childhood sleep at different developmental stages within the same sample of children to see if there’s an impact on later substance use, which few studies have investigated. They focused on two different facets of sleep health – total duration of sleep and time of sleep or bedtime. The researchers explained that if children, especially school-aged children, go to bed later, it could affect their ability to sleep well.

“Sleep is multifaceted. It’s important for children because it helps with growth and development. The brain is more plastic during younger ages and you want healthy sleep to support neural development,” said David Reichenberger, co-lead author and who earned his doctoral degree in biobehavioural health at Penn State during the time of the research. “Poor sleep health could have downstream effects on their physical health as well as decision making, which could in turn be related to their decision to engage in substance use.”

The study drew on data from 1514 children in the Future of Families and Child Wellbeing Study, a diverse longitudinal birth cohort of children from 20 cities across the United States. Parents reported their child’s regular weekday bedtime at ages three, five and nine. They also reported their child’s sleep duration at ages five and nine.

When the research team evaluated the relationship between childhood bedtime and sleep duration with future alcohol and marijuana use as teens, they found a longitudinal association. Teens were 45% more likely to try alcohol by age 15 if they had a later bedtime at age nine when compared to other children with earlier bedtimes at age nine. However, bedtime at age five wasn’t associated with future alcohol use, nor was sleep duration at ages five or nine. When it came to marijuana use, later bedtime at age five was associated with 26% increased odds of trying marijuana by age 15, while sleeping an hour less at age nine was associated with 19% increased odds of trying marijuana by age 15.

The research team also examined data from adolescents at age 15, who self-reported their bedtime, sleep duration and alcohol and marijuana use. They found that teens with a later bedtime had a 39% greater chance of drinking alcohol and a 34% greater chance of trying marijuana. Sleeping one hour less was associated with 28% increased odds of ever trying alcohol but wasn’t associated with marijuana use.

“Sleep at ages closer to adolescence is the most crucial in terms of future substance use risk. It’s that stage of development when children are rapidly changing and their brain is maturing,” Reichenberger said, noting that previous research by other groups suggests that shorter sleep duration and later bedtimes may increase impulsivity and impair decision making, which could influence substance use choices.

The findings highlight the critical role of sleep across multiple aspects of long-term health and wellbeing, researchers said. For school-age children, creating an environment that’s conducive for sleep and establishing an age-appropriate bedtime are key elements for cultivating good sleep.

“Exploring the connection between sleep and substance use is a critical area of research because we continue to struggle with an epidemic of opioid addiction and substance use,” Chang said. “It’s an important area to continue to research and to disseminate our research findings to the broader population, families and health care professionals.”

Source: University of Pennsylvania

Faster Detection of Pancreatic Cancer

Glycopeptide probes detect tumour-associated antibodies in blood samples

Pancreatic cancer. Credit: Scientific Animations CC BY-SA 4.0

Pancreatic cancer is one of the most lethal forms of cancer, primarily because it is usually diagnosed very late. Current markers are too insensitive and unspecific for early detection screenings. In the journal Angewandte Chemie, a research team has now introduced a new method that could lead to a significantly more precise and reliable diagnosis. It is based on the selective detection of specific antibodies in blood samples.

Tumours produce certain proteins (tumour-associated antigens) that draw the attention of our constantly “patrolling” immune system and trigger an immune response. As a consequence, antibodies directed against the tumours (tumour-associated autoantibodies) are formed, circulating in the blood at very early stages of the disease – which makes them useful for early detection. An international team led by Roberto Fiammengo and Giovanni Malerba at the University of Verona (Italy) as well as Alfredo Martínez at the Center for Biomedical Research of La Rioja (Logroño, Spain) and Francisco Corzana at the Universidad de La Rioja, has now developed an approach to diagnostic testing for pancreatic cancer that is based on the detection of such special tumour-associated autoantibodies.

They chose to use autoantibodies directed against the tumour-associated form of mucin-1 (TA-MUC1). Mucin-1 is a heavily glycosylated protein (a protein with sugar components) that occurs, for example, in glandular tissue. In many types of tumours, including pancreatic cancer, it is found in significantly elevated concentrations. In addition, the pattern of glycosylation is different from the normal form. The team’s goal was to detect autoantibodies that are directed specifically against TA-MUC1 and are a clear indicator of pancreatic cancer.

Based on structural analyses and computer simulations of known antibodies against TA-MUC1 (SM3 and 5E5), the team designed a collection of synthetic glycopeptides that mimic different segments (epitopes) of TA-MUC1. They also made unnatural modifications to increase the chances of identifying autoantibody subgroups indicative of the disease. The team immobilised these model antigens on gold nanoparticles achieving probes suitable for a serological assay (dot-blot assay). The diagnostic assay was validated with real samples from patients with pancreatic cancer and a healthy control group. Some of the nanoparticle probes could differentiate very well between samples from diseased and healthy individuals demonstrating they detected tumour associated autoantibodies. Notably, these specific autoantibodies displayed significantly better correct positive/false positive ratios than current clinical biomarkers for pancreatic cancer.

Probes with smaller glycopeptide antigens that correspond to only a single epitope, gave better results than larger probes that mimic multiple epitopes – an advantage for easier synthetic production. A short glycopeptide with an unnatural modification to its sugar component was found to be particularly effective for the detection of discriminating autoantibodies. This new structure-based approach could help in the selection of autoantibody subgroups with higher tumour specificity.

Source: Wiley

Could a New Role for Propofol be Treating Epilepsy?

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The general anaesthetic propofol may hold the keys to developing new treatment strategies for epilepsy and other neurological disorders, according to a study led by researchers at Weill Cornell Medicine and Linköping University in Sweden.

In their study, published in Nature, the researchers determined the high-resolution structural details of how propofol inhibits the activity of HCN1, an ion channel protein found on many types of neurons. Drug developers consider inhibiting HCN1 a promising strategy for treating neurologic disorders including epilepsy and chronic pain. The researchers also found, to their surprise, that when HCN1 contains either of two epilepsy-associated mutations, propofol binds to it in a way that restores its functionality.

“We might be able to exploit propofol’s unique way of binding to HCN1 for the treatment of these drug-resistant epilepsies and other HCN1-linked disorders, either by directly repurposing propofol or by designing new, more selective drugs that have the same mechanism of action,” said study co-senior author Dr Crina Nimigean, professor of physiology and biophysics in anaesthesiology at Weill Cornell Medicine.

The study’s first author was Dr Elizabeth Kim, a postdoctoral research associate in the Nimigean laboratory.  

HCN ion channels in humans come in four basic forms, HCN1 to HCN4, and are found especially on cells in the heart and nervous system. They work as switches to control the electrical voltage across the cell membrane, opening to admit an inward flow of positively charged potassium and sodium ions – thus “depolarising” the cell – when the voltage reaches a certain threshold. This function underpins much of the rhythmic activity of brain and heart muscle cells, which is why HCN channels are also called pacemaker channels.

In the study, the researchers used cryo-electron microscopy and other methods to determine, at near-atomic scale, how propofol reduces HCN1 activity – which it does with selectivity for HCN1 over other HCNs. They found that the drug inhibits HCN1 by binding within a groove between two elements of the channel protein’s central pore structure, making it harder for the pore to open.

As they investigated propofol’s action on HCN1, the researchers examined how the drug affects different known mutants of the channel, including mutants that leave it excessively open and are associated with hard-to-treat epilepsy syndromes such as early infantile epileptic encephalopathy (EIEE). The researchers were surprised to find that for two different HCN1 mutations that cause EIEE, propofol restores the mutant channels to normal or near-normal function.

From their experiments, the researchers derived a model in which the mutations decouple HCN1’s voltage-sensing and pore mechanisms, while propofol effectively recouples them, allowing membrane voltage to control ion flow again.

The results suggest at least two possibilities for translation to therapies. One is simply to use propofol, an existing, approved drug, to treat these HCN1-mutation epilepsies and potentially other HCN1-linked disorders. Propofol is a potent anesthetic that requires careful monitoring by anaesthesiologists, but it might be able to restore HCN1 function at doses below those used for general anaesthesia.

The other possibility, the researchers said, is to use the new structural data on propofol’s binding to design modified, non-anesthetic versions of propofol, or even completely different compounds, that bind to HCN1 with a similar effect but much more selectively—in other words, without binding to other channels, including other HCNs, in the body and thereby potentially causing unwanted side effects.

“For that we will need a better understanding of how propofol inhibits HCN1 better than other HCN channels,” Dr Kim said.

Source: Weill Cornell Medicine