Study reveals a significant link, suggesting that managing metabolic syndrome may help prevent cancer.
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New research indicates that individuals with persistent and worsening metabolic syndrome – which encompasses conditions such as high blood pressure, elevated blood sugar, excess abdominal fat, and abnormal cholesterol – face an elevated risk of developing various types of cancer. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.
In the study, 44 115 adults in China with an average age of 49 years were categorised into 4 different trajectories based on trends from 2006 (the time of the first physical exam) to 2010: 10.56% exhibited a low-stable pattern and maintained low metabolic syndrome scores; 40.84% exhibited a moderate-low pattern and maintained moderate to low metabolic syndrome scores; 41.46% exhibited a moderate-high pattern and consistently maintained moderate to high metabolic syndrome scores; and 7.14% exhibited an elevated-increasing pattern in which initially elevated metabolic syndrome scores increased over time.
During the follow-up period of 2010–2021, with a median follow-up of 9.4 years, there were 2271 cancer diagnoses among participants. Compared with participants with a low-stable trajectory pattern, those with an elevated-increasing trajectory pattern had 1.3-, 2.1-, 3.3-, 4.5-, 2.5-, and 1.6-times higher risks of developing any cancer, breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer, respectively.
Even when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined, the elevated-increasing trajectory pattern group had higher risks of developing all cancer types.
Also, participants with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of developing breast, endometrial, colon, and liver cancer, whereas the risk of kidney cancer was predominantly observed among participants with persistently high scores but without chronic inflammation.
“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” said senior author Han-Ping Shi, MD, PhD, of Capital Medical University, in Beijing. “Our study can guide future research into the biological mechanisms linking metabolic syndrome to cancer, potentially resulting in targeted treatments or preventive strategies. Formal evaluation of these interventions will be needed to determine if they are able to modulate cancer risk.”
A new study has tricked bacteria into sending death signals to stop the growth of biofilms that lead to deadly infections. The discovery by Washington State University researchers could someday be harnessed as an alternative to antibiotics for treating difficult infections.
Reporting in the journal,Biofilm, the researchers used the messengers, which they named death extracellular vesicles (D-EVs), to reduce growth of the bacterial communities by up to 99.99% in laboratory experiments.
“Adding the death extracellular vesicles to the bacterial environment, we are kind of cheating the bacteria cells,” said Mawra Gamal Saad, first author on the paper and a graduate student in WSU’s Gene and Linda Voiland School of Chemical Engineering and Bioengineering.
“The cells don’t know which type of EVs they are, but they take them up because they are used to taking them from their environment, and with that, the physiological signals inside the cells change from growth to death.”
Bacterial resistance is a growing problem around the world. In the US, at least 2 million infections and 23 000 deaths are attributable to antibiotic-resistant bacteria each year, according to the U.S. Centers for Disease Control.
When antibiotics are used to treat a bacterial infection, some of the bacteria can hide within their tough-to-penetrate biofilm. These subpopulations of resistor cells can survive treatment and are able to grow and multiply, resulting in chronic infections.
“They are resistant because they have a very advanced and well-organised adaptive system,” said Saad.
“Once there is a change in the environment, they can adapt their intracellular pathways very quickly and change it to resist the antibiotics.”
In their new study, the researchers discovered that the extracellular vesicles are key to managing the growth of the protective biofilm.
The vesicles, tiny bubbles from 30 to 50nm or about 2000 times smaller than a strand of hair, shuttle molecules from cells, entering and then re-programming neighbouring cells and acting as a cell-to-cell communications system.
As part of this study, the researchers extracted the vesicles from one type of bacteria that causes pneumonia and other serious infections.
They determined that the bacteria initially secrete vesicles, called growth EVs, with instructions to grow its biofilm, and then later, depending on available nutrients, oxygen availability and other factors, send EVs with new instructions to stop growing the biofilm.
The researchers were able to harness the vesicles with the instructions to stop growth and use them to fool the bacteria to kill off the biofilm at all stages of its growth.
Even when the biofilms were healthy and rapidly growing, they followed the new instructions from the death EVs and died. The death EVs can easily penetrate the biofilm because they are natural products secreted by the bacteria, and they have the same cell wall structure, so the cells don’t recognise them as a foreign enemy.
“By cheating the bacteria with these death EVs, we can control their behaviour without giving them the chance to develop resistance,” said Saad.
“The behavior of the biofilm just changed from growth to death.”
WSU Professor and corresponding author Wen-Ji Dong, who has been studying the vesicles for several years initially thought that all of the bacterial-secreted vesicles would promote cell growth.
The researchers were surprised when they found that older biofilms provided instructions on shutting themselves down.
“So now we’re paying attention to the extracellular vesicles secreted by older biofilms because they have therapeutic potential,” he said.
An innovative treatment significantly increases the survival of people with malignant mesothelioma, a rare but rapidly fatal type of cancer with few effective treatment options, according to results from a clinical trial led by Queen Mary University of London and published in JAMA Oncology.
The phase 3 clinical trial, led by Professor Peter Szlosarek at Queen Mary and sponsored by Polaris Pharmaceuticals, has unveiled a breakthrough in the treatment of malignant pleural mesothelioma (MPM), a rare and often rapidly fatal form of cancer with limited therapeutic options.
The ATOMIC-meso trial, a randomised placebo-controlled study of 249 patients with MPM, found that a treatment – which combines a new drug, ADI-PEG20, with traditional chemotherapy – increased the median survival of participants by 1.6 months, and quadrupled the survival at 36 months, compared to placebo-chemotherapy.
The findings are significant, as MPM has one of the lowest 5-year survival rates of any solid cancer of around 5-10%. This innovative approach marks the first successful combination of chemotherapy with a drug that targets cancer’s metabolism developed for this disease in 20 years.
MPM is a rare, aggressive cancer that affects the lining of the lungs and is associated with exposure to asbestos. It’s usually treated with potent chemotherapy drugs, but these are seldom able to halt the progression of the disease.
The premise behind this new drug treatment is elegant in its simplicity – starving the tumour by cutting off its food supply. All cells need nutrients to grow and multiply, including amino acids like arginine. ADI-PEG20 works by depleting arginine levels in the bloodstream. For tumour cells that can’t manufacture their arginine due to a missing enzyme, this means their growth is thwarted.
The ATOMIC-meso trial is the culmination of 20 years of research at Queen Mary’s Barts Cancer Institute that began with Professor Szlosarek’s discovery that malignant mesothelioma cells lack a protein called ASS1, which enables cells to manufacture their own arginine. He and his team have since dedicated their efforts to using this knowledge to create an effective treatment for patients with MPM.
Professor Szlosarek said: “It’s truly wonderful to see the research into the arginine starvation of cancer cells come to fruition. This discovery is something I have been driving from its earliest stages in the lab, with a new treatment, ADI-PEG20, now improving patient lives affected by mesothelioma. I thank all the patients and families, investigators and their teams, and Polaris Pharmaceuticals for their commitment to defining a new cancer therapy.”
There are ongoing studies assessing ADI-PEG20 in patients who have sarcoma or glioblastoma multiforme and other cancers dependent on arginine. The success of this novel chemotherapy in MPM also suggests that the drug may be of benefit in the treatment of multiple other types of cancer.
Spotlight visits Rahima Moosa Mother and Child Hospital and sees progress for the struggling hospital but also the reality that there’s a long road ahead to undo what a health ombud report suggests has been years of neglect and poor management.
Rahima Moosa Mother and Child Hospital serves up to 2 300 people admitted per month as well as 10 000 outpatients each month. (Photo: Denvor de Wee/Spotlight)
By Ufrieda Ho for Spotlight
It’s been a year since a damning Health Ombud’s report on the Rahima Moosa Mother and Child Hospital (RMMCH) was released. This month also marks the end of the last deadline the Gauteng Department of Health had to act on recommendations in the report.
At 80 years old, RMMCH is an iconic landmark on the western edge of Johannesburg. But it has gone from a one-time outlier for excellence to being in steady decline, marked by what the Ombud’s report criticised as incompetent leadership, neglect and crumbling infrastructure.
In May 2022, the hospital suffered a public low point when paediatric gastroenterologist, Dr Tim de Maayer, penned an open letter, slamming multiple failings at the facility. Public outcry from the letter, complaints from hospital users, and a widely circulated video of pregnant mothers sleeping on hospital corridor floors prompted the ombud’s investigation.
When Spotlight visited the hospital at the end of February (2024), there were positive outward signs that recent maintenance work had been completed, per the Ombud’s recommendations. Some areas have been painted and surfaces where underground sewer pipes had to be unblocked have also been tarred. The stench from overflowing sewage appears to be a thing of the past. Renovations to the antenatal care ward, shown in the video that went viral, are also near completion and the ward is expected to be operational again by the middle of March.
More signs that RMMCH is blipping on radars again include a new granite plaque at the entrance ready to be unveiled to commemorate the hospital in its 80th year. On noticeboards were flyers that advertised a community fun-walk for the end of February. It was an event intended to “reconnect” hospital staff with the immediate community it serves.
The hospital is also part of the roll-out of the provincial health information system (HIS) and admin staff were seen enrolling new patients on the system. The HIS is a long-awaited system to modernise patient file storage and make patient files accessible at facilities province-wide. Spotlight previously reported on the system.
These encouraging advances since the Ombud’s investigation get the thumbs up from hospital insiders. But they flag that even though the Gauteng Department of Health has announced a six-year renewal plan for the hospital and R53 million was approved in December 2023 for the next phase of renovations, the department is playing catch-up and still dragging its feet.
CT scan empty promises
For Dr Z, the biggest of her current concerns is that the hospital’s CT scan has not been in operation for the past 14 months. Dr Z asked not to be named because of the risk of victimisation.
“We have to beg other hospitals to do our scans. So even when you have a patient who actually needs a CT scan, you think twice – you ask yourself do they really, really need it or should you just watch them for another couple of months. It’s very demoralising and we keep hearing empty promises from management,” Dr Z says.
A shortage of clerical staff means clerks are shared between departments, resulting in inevitable administrative glitches and delays, Dr Z says.
There is also a growing need for child mental health services but the hospital doesn’t have in-patient psychiatry services and only has sessional psychological services.
“We serve an ever bigger community that has changing needs but our infrastructure has stayed the same and our staff numbers have not increased,” says Dr Z. The doctor has worked at RMMCH for nearly two decades – “my second home” she calls it.
The hospital has around 1200 staff members. They serve up to 2300 people admitted per month as well as 10 000 outpatients each month.
Dr Z tries to stay hopeful, saying “we look to the positive things and we do what we can”, but RMMCH can be a daunting place to work. Safety and security has resurfaced as a concern this February. This comes on the back of a car hijacking that took place in the hospital’s parking area at the beginning of the month. The Ombud’s report also looked into the hijacking of an intern’s car that took place in its investigation period.
Parking too is a daily frustration – there are only 300 parking spots for staff on the hospital campus but at least 400 vehicles that need a place to park at peak times. Visitors are told to park on the streets.
‘Mr Fixer’
Acting CEO of the hospital Dr Arthur Manning met with Spotlight to answer questions put to him and to the Gauteng Department of Health.
Manning took up the job in September 2022 as part of the Ombud’s recommendation to redeploy the previous CEO, Dr Nozuko Mkabayi, whom the government oversight body found to be a dismal failure.
Manning calls himself “a fixer”. His role, he recognises, has been to help stop the slide for RMMCH, also to boost staff morale, restore communication channels and regain the community’s trust in the facility.
“We are a system under pressure and we know there is burnout and low morale but we have improved counselling support and we try to recognise and thank people. We held a nurse’s awards dinner last year exactly for these reasons,” he says.
Manning says the hospital organogram was last updated in 2006, but he has submitted a revised one to the Gauteng Department of Health. It makes the case for more admin and support staff, more junior and training doctor posts and bolstering psychiatric and psychological services. These, he says, are especially necessary because services for children are particularly neglected.
The broken CT scanner at Rahima Moosa Mother and Child Hospital. (Photo: Denvor de Wee/Spotlight)
On the matter of the CT scanner, he says “procurement is underway”. It’s a planning failure that the machine is five years beyond its expected lifespan and was not replaced sooner, resulting in the current gap. Manning says the Gauteng Department of Health is now piggybacking on Limpopo’s procurement contract. Piggybacking refers to provisions in the Public Finance Management Act, that under certain conditions, allow a department in one province to procure goods and services via a contract that a department in another province has concluded with a service provider.
According to Manning, the Gauteng province is currently concluding an X-ray equipment tender that has delayed the procurement of the CT scanner for RMMCH. “Without a tender in place, procurement is more difficult,” he says. Approval to use Limpopo’s tender contract cuts out some red tape and means the CT scanner and maintenance contract has been secured at the price of R30 million. By May, he says, the hospital will also have an MRI-scanning facility.
Staff helps to spruce up waiting area
Manning has been credited by some for shifting morale and competently overseeing the interventions set out by the Ombud’s report. On a hospital walkthrough with Spotlight, he engages casually with staff and patients. He’s also evidently proud of staff-driven initiatives to improve the hospital experience for patients. He points out a freshly painted waiting area in one of the departments where children are playing with new toys and crawling on bright green astro turf. More than half the money for this project came from doctors and nurses raising funds cycling and running in race events in the city.
Keeping staff motivated means their concerns and working conditions – including the parking problem and safety and security – have to be priorities, he says.
Cars are double and triple-parked in the overcrowded staff parking area. Currently, informal management of this is done via Whatsapp groups. People on the groups are notified to move their cars as spots free up. Manning says the hospital is working to secure nearby grounds for additional parking. On safety and security, he says the hospital has stepped up collaboration with local police and the community policing forums to increase patrolling around the hospital especially around shift changes. He adds: “We have expanded our CCTV camera coverage, requested for armed security control and we’re exploring panic button systems.”
A bigger budget and a permanent CEO
There are two key outstanding issues from the Ombud’s report. The first is reclassification of the hospital that is also an academic and training hospital, from a regional facility to a tertiary hospital.
“This is something that involves national, but when reclassification is done it will means RMMCH’s budgets and grants will be adjusted and we will be able to do so much more,” says Manning.
The second issue is the appointment of a permanent CEO, which Manning says is “being handled by central office”. He side-steps a question on whether his name is in the mix. It’s expected that an announcement on the new CEO will take place in April.
Professor Ashraf Coovadia is academic head of Paediatrics and Child Health at Wits University and heads up this department at RMMCH. He says Manning has “been good for RMMCH” but he says above the level of CEO, it’s the Gauteng Department of Health that needs to get its house in order . He says there has been a lack of communication, consultation, transparency and decisive action from the Gauteng Department of Health for years.
“A CEO can do only so much. When we have having acting heads in so many departments who are in acting positions for forever, it’s a joke. It means decisions don’t get made or decisions don’t get made for the long run and this compromises how the hospital is run and the care we give patients,” he says.
He adds that when there is less “hospital floor” consultation and more bureaucratic centralisation from the department it alienates doctors and nurses. “It becomes more and more difficult to try to motivate especially junior doctors who start off wanting to give back to the public health service but become so frustrated they don’t stay.”
Back to the 1900s
Like Dr Z, Coovadia highlights the CT scan issue, as well as the long delays and the excuses for the delays.
“Working without a scanner takes us back to the 1900s; we are not practising modern medicine and we are not able to diagnose patients early enough,” he says.
Coovadia adds that even though water and electricity supply issues at RMMCH have improved, infrastructure fixes remain patchy. “There are fewer issues of burst pipes and flooding, but it’s still happening.”
Coovadia has been with the hospital for 26 years, he knows better than most the precariousness of the situation and why the hospital is not yet out of the woods. He says: “The negative attention on the hospital did bring about some positive change. But it can make you cry when you see the slide over the last ten years… The hospital is not collapsing, but there are daily collapses.”
NOTE: Coovadia is on the board of SECTION27. Spotlight is published by SECTION27, but is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.
Investing in women’s health is not only a moral imperative; it makes economic sense. International Women’s Day (8 March 2024) should serve as a rallying cry that it is time to turn talk into action – and a lasting commitment to regenerating women’s health.
“Shaping the private and public health agenda through increased advocacy and awareness, with governments and medical professionals putting women’s health on – and higher up – the agenda and targeting sources of stigma and bias – this is what we need to do right now,” says Jo Pohl, Associate Director at global management consultancy Kearney.
Pohl was speaking (this week) on the eve of International Women’s Day, and following an event organised by Kearney to commemorate the day. Guests listened to the story of ‘Tina B’, the longest-surviving heart and bilateral lung transplant recipient in Africa (during a gathering at Kearney’s Johannesburg offices on Wednesday 6 March 2024).
The event explored Tina’s resilience, the challenges she faced, the odds she beat, and just how different her journey could have been with the advent of Artificial Intelligence (AI) in donor healthcare decision-making.
She shared her opinion on the use of AI in selecting organ donors. Tina told guests at the event that she believes if AI had to decide whether she should receive her surgery or not, it would have decided against her based on inherent biases or rather what the AI was asked to solve for.
According to her, AI would have assessed the state of her lungs and heart and potentially rejected her as a candidate for organ donation. Since she needed three organs, AI would have viewed her as one, high risk candidate versus the potential to save three “better” candidates.
The human element – from intuition to hope and optimism – is key. She told guests that her doctors echoed the same in terms of leveraging experience, expertise, and an understanding of a patient’s mindset.
“I am not an expert in AI, but I am an expert in being a patient,” she said. “AI could help inform options but needs to be questioned, and experienced doctors need to be able to apply their human intuition in any results.”
Typically, there are over 4000 people on the organ transplant waiting list at any given time, with only 0.2% of the population opting-in for organ donation. These kinds of numbers lead to questions such as “how is one candidate chosen over another and why”, questions that become even more important as we increasingly incorporate AI in healthcare decisions.
“Just think of the implications for healthcare professionals, researchers, and policymakers to develop and implement AI in healthcare ethically, equitably, and inclusively, if we consider transplant patients,” says Pohl.
“AI in healthcare should be used to benefit all members of society, regardless of gender, race, or socio-economic status. How can we co-create a world where everyone is seen, heard and the human considered in healthcare decision-making,” says Theo Sibiya, Kearney’s Africa MD.
“There needs to be a deliberate focus on keeping women front of mind and lending our expertise to continue breaking down barriers such as the gender health gap by redesigning healthcare that can put women first,” he adds.
Tina B has now become an advocate for organ donation and aims to help others going through the waiting process. She told guests of her experience of having to wait three years on the organ donor waiting list.
“You start to lose hope. You get excited to get on the list, but time drags on, and your body starts to fail you…it is a very dark place. I was tired of fighting to breathe, to stay awake; I remember saying to my God if you don’t give me a transplant, then take me home.”
AI has the potential to revolutionise the healthcare industry. With the ability to analyse large amounts of data quickly, AI can help healthcare professionals make more informed decisions, improving patient outcomes. It is an “and” versus “or” proposition.
“We need to be mindful, however, of inherent gender biases, overcome programming that favours males, and address flaws in the interpretation of data that exclude human perspectives. Doing so can make AI in healthcare more representative and inclusive,” says Sibiya.
Pohl explains that a women-informed lens is essential to ensuring equity and inclusivity in AI development and application.
“Regenerate is Kearney’s answer to “what’s next” in a post-resilience world and a timely approach to how businesses can and should be ready for the future. Tina B is a living example of regeneration, her story amplifies our Kearney commitment to a global campaign to “be the difference” for women’s health which we launched in Davos earlier this year,” says Sibiya.
“This amplifies our vision, rooted in a regenerative mindset that recognises the interconnectedness of our actions and their impact on the world around us, including how we make and execute healthcare and people decisions.”
As part of this vision, an open letter was released by Kearney and FemTechnology during the World Economic Forum Annual Meeting on behalf of the Redesigning Healthcare with Women in Mind signatories.
The letter is addressed to all those within the healthcare ecosystem whose innovations have impact and decisions have power: from pharma, biotech, and medtech firms to investors, tech companies, and consumer health players serving women and girls.
The signatories call for a commitment to challenge institutional gender inequalities and shape the future of public and private healthcare for those it has failed for far too long.
Replacing table salt with a salt substitute can reduce incidence of hypertension in older adults without increasing their risk of hypotension episodes, according to a recent study in the Journal of the American College of Cardiology. Participants using a salt substitute had a 40% lower incidence and likelihood of experiencing hypertension compared to those who used regular salt.
One of the most effective ways to reduce hypertension risk, one of the world’s leading health risks, is to reduce sodium intake. This study looks at salt substitutes as a better solution to control and maintain healthy blood pressure than reducing salt alone.
“Adults frequently fall into the trap of consuming excess salt through easily accessible and budget-friendly processed foods,” said Yangfeng Wu, MD, PhD, lead author of the study and Executive Director of Peking University Clinical Research Institute in Beijing, China.
“It’s crucial to recognise the impact of our dietary choices on heart health and increase the public’s awareness of lower-sodium options.”
Researchers in this study evaluated the impact of sodium reduction strategies on blood pressure in elderly adults residing in care facilities in China.
While previous studies prove that reducing salt intake can prevent or delay new-onset hypertension, long-term salt reduction and avoidance can be challenging.
The DECIDE-Salt study included 611 participants 55 years or older from 48 care facilities split into two groups: 24 facilities (313 participants) replacing usual salt with the salt substitute and 24 facilities (298 participants) continuing the use of usual salt.
All participants had blood pressure <140/90mmHg and were not using anti-hypertension medications at baseline.
The primary outcome was participants who had incident hypertension, initiated anti-hypertension medications or developed major cardiovascular adverse events during follow-up.
At two years, the incidence of hypertension was 11.7 per 100 people-years in participants with salt substitute and 24.3 per 100 people-years in participants with regular salt.
People using the salt substitute were 40% less likely to develop hypertension compared to those using regular salt. Furthermore, the salt substitutes did not cause hypotension, which can be a common issue in older adults.
“Our results showcase an exciting breakthrough in maintaining blood pressure that offers a way for people to safeguard their health and minimise the potential for cardiovascular risks, all while being able to enjoy the perks of adding delicious flavour to their favourite meals,” Wu said.
“Considering its blood pressure – lowering effect, proven in previous studies, the salt substitute shows beneficial to all people, either hypertensive or normotensive, thus a desirable population strategy for prevention and control of hypertension and cardiovascular disease.”
Limitations of the study include that it is a post-hoc analysis, study outcomes were not pre-specified and there was a loss of follow-up visits in many patients.
Analyses indicated that these missing values were at random, and multiple sensitivity analyses supports the robustness of the results.
In an accompanying editorial comment, Rik Olde Engberink, MD, PhD, researcher, nephrologist and clinical pharmacologist at Amsterdam University Medical Center’s Department of Internal Medicine, said the study provides an attractive alternative to the failing strategy to reduce the intake of salt worldwide, but questions and effort remain.
“In the DECIDE-Salt trial, the salt substitute was given to the kitchen staff, and the facilities were not allowed to provide externally sourced food more than once per week,” Olde Engberink said. “This approach potentially has a greater impact on blood pressure outcomes, and for this reason, salt substitutes should be adopted early in the food chain by the food industry so that the sodium-potassium ratio of processed foods will improve.”
A flurry of recent studies has found that microplastics are present in virtually everything we consume, from bottled water to meat and plant-based food. Now, University of New Mexico Health Sciences researchers have used a new analytical tool to measure the microplastics present in human placentas.
In a study published in the journal Toxicological Sciences, a team led by Matthew Campen, PhD, Regents’ Professor in the UNM Department of Pharmaceutical Sciences, reported finding microplastics in all 62 of the placenta samples tested, with concentrations ranging from 6.5 to 790 micrograms per gram of tissue.
Although those numbers may seem small, Campen is worried about the health effects of a steadily rising volume of microplastics in the environment.
For toxicologists, “dose makes the poison,” he said. “If the dose keeps going up, we start to worry. If we’re seeing effects on placentas, then all mammalian life on this plant could be impacted. That’s not good.”
In the study, Campen and his team, partnering with colleagues at the Baylor College of Medicine and Oklahoma State University, analyzed donated placenta tissue. In a process called saponification, they chemically treated the samples to “digest” the fat and proteins into a kind of soap.
Then, they spun each sample in an ultracentrifuge, which left a small nugget of plastic at the bottom of a tube. Next, using a technique called pyrolysis, they put the plastic pellet in a metal cup and heated it to 600 degrees Celsius, then captured gas emissions as different types of plastic combusted at specific temperatures.
“The gas emission goes into a mass spectrometer and gives you a specific fingerprint,” Campen said. “It’s really cool.”
The researchers found the most prevalent polymer in placental tissue was polyethylene, which is used to make plastic bags and bottles. It accounted for 54% of the total plastics. Polyvinyl chloride (better known as PVC) and nylon each represented about 10% of the total, with the remainder consisting of nine other polymers.
Marcus Garcia, PharmD, a postdoctoral fellow in Campen’s lab who performed many of the experiments, said that until now, it has been difficult to quantify how much microplastic was present in human tissue. Typically, researchers would simply count the number of particles visible under a microscope, even though some particles are too small to be seen.
With the new analytical method, he said, “We can take it to that next step to be able to adequately quantify it and say, ‘This is how many micrograms or milligrams,’ depending on the plastics that we have.”
Plastic use worldwide has grown exponentially since the early 1950s, producing a metric ton of plastic waste for every person on the planet. About a third of the plastic that has been produced is still in use, but most of the rest has been discarded or sent to landfills, where it starts to break down from exposure to ultraviolet radiation present in sunlight.
“That ends up in groundwater, and sometimes it aerosolizes and ends up in our environment,” Garcia said. “We’re not only getting it from ingestion but also through inhalation as well. It not only affects us as humans, but all off our animals — chickens, livestock — and all of our plants. We’re seeing it in everything.”
Campen points out that many plastics have a long half-life — the amount of time needed for half of a sample to degrade. “So, the half-life of some things is 300 years and the half-life of others is 50 years, but between now and 300 years some of that plastic gets degraded,” he said. “Those microplastics that we’re seeing in the environment are probably 40 or 50 years old.”
While microplastics are already present in our bodies, it is unclear what health effects they might have, if any. Traditionally, plastics have been assumed to be biologically inert, but some microplastics are nanometres in size and are capable of crossing cell membranes, he said.
Campen said the growing concentration of microplastics in human tissue might explain puzzling increases in some types of health problems, such as inflammatory bowel disease and colon cancer in people under 50, as well as declining sperm counts.
The concentration of microplastics in placentas is particularly troubling, he said, because the tissue has only been growing for eight months (it starts to form about a month into a pregnancy). “Other organs of your body are accumulating over much longer periods of time.”
Campen and his colleagues are planning further research to answer some of these questions, but in the meantime he is deeply concerned by the growing production of plastics worldwide.
“It’s only getting worse, and the trajectory is it will double every 10 to 15 years,” he said. “So, even if we were to stop it today, in 2050 there will be three times as much plastic in the background as there is now. And we’re not going to stop it today.”
Although several studies have linked smoking during pregnancy with neurodevelopmental disorders, the results of behavioural experiments in mice prenatally exposed to nicotine have been inconsistent. In a recent study, scientists from Japan developed a deep learning-based framework to automatically observe and classify mice behaviour in such experiments, producing more accurate and unbiased results. In their results, published recently in Cells, they show that prenatal exposure to nicotine could increase the risk of autism spectrum- and attention deficit/hyperactivity disorders in newborns.
The fact that smoking is a risk factor for several diseases, including cancer, stroke, and diabetes, has been known for approximately half a century. However, over the past few decades, scientists have brought to light many of the detrimental effects of smoking during pregnancy, linking this habit to high infant mortality, failed delivery, and low body weight at birth. In addition, recent studies suggest that prenatal nicotine exposure (PNE) may be related to neurodevelopmental disorders, such as attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).
For a long time now, scientists have used animal models (like rodents) to understand how PNE leads to neurodevelopmental disorders. By carefully analysing the behaviour of rodents, they can infer whether PNE is causing neurological changes and the brain regions affected by it; this can later be confirmed through histological analyses.
Unfortunately, thus far, studies on behavioural changes induced by PNE in mice have shown varied results, some of which are contradictory. Although there could be multiple reasons behind these discrepancies, human error and bias are prime suspects. In general, the assessment of complex animal behaviours, especially social interactions, relies on the efforts of human observers, which introduces a baseline level of subjectivity that is hard to dispel. But what if we can leverage artificial intelligence (AI) to produce more accurate and unbiased results from observations of PNE mice behaviour?
In this study , researchers from the Department of Molecular and Cellular Physiology at the Shinshu University School of Medicine, including graduate student Mengyun Zhou, Assistant Professor Takuma Mori, and Professor Katsuhiko Tabuchi, developed and trained a deep learning-based system to automatically analyse footage from behavioural experiments on mice. They used this tool to explore the behavioural changes induced by PNE in mice without observer biases, seeking to shed light on the link between nicotine and neurodevelopmental disorders.
The proposed AI-based framework relied on a combination of two well-established open-source toolkits, namely DeepLabCut and Simple Behavioral Analysis (SimBA). “AI tools can label the body parts of animals in a markerless video footage and precisely estimate their poses using supervised machine learning,” explains Prof Tabuchi. “Since animal behaviours are defined as a specific arrangement of body parts over a short period of time, deep-learning toolkits like SimBA can use the pose estimations obtained with DeepLabCut to classify different types of animal behaviours.”
After reaching an optimal training protocol for their framework using manually labelled data, the researchers conducted several experiments using PNE and control mice, looking for indicators of ADHD- and ASD-like behaviours. First, they carried out cliff avoidance reaction tests, which are used to test impulsivity. In these tests, they placed the subject mouse on top of a slightly elevated platform and took note, both manually and with the AI system, of how long the mouse waited before jumping down the platform. The test results suggested that PNE mice are more impulsive, a behavioural feature of ADHD in humans.
They also tested the working memory of mice using a Y-shaped maze and counted the number of times each mouse spontaneously switched from one arm of the maze to another. “We observed a decrease in the spontaneous alteration in PNE mice, suggesting that their working memory was altered, which is another behavioural feature of ADHD,” comments Mengyun Zhou. “These results suggest prenatal exposure to nicotine may cause ADHD in mice, which is consistent with clinical reports in humans.”
Finally, the researchers conducted open-field and social-interaction experiments, which represented the main challenge for their AI-based system. In these experiments, the researchers observed either one or two mice behaving freely in a large enclosure and looked for indicators of anxiety and social behaviours, such as grooming and following. Interestingly, PNE mice exhibited social behavioural deficits and increased anxiety which are features of ASD. Subsequent histological analysis of hippocampal brain tissue confirmed decreased neurogenesis, a hallmark of ASD. Thus, it appears that smoking may not only increase the risk of ADHD, but also ASD.
Worth noting, the results obtained using the AI-based system were highly reliable, as Prof Tabuchi highlights: “We validated the accuracy of our behavioural analysis framework by drawing a careful comparison between the results generated by the model and behaviour assessments made by multiple human annotators, which is considered the gold standard.” These analyses cement the potential of the proposed approach and showcase its capabilities for many types of behavioural studies.
With any luck, further efforts will pave the way to a solid understanding of mechanisms behind neurodevelopmental disorders like ASD and ADHD, ultimately leading to better diagnostic tools and therapeutic methods.
In a potentially game-changing development, scientists at Virginia Tech have revealed a new understanding of sometimes fatal viral infections that affect the heart.
The focus has mostly been on myocarditis, which is often triggered by the body’s immune response to a viral infection. Now, a new study led by James Smyth, associate professor at the Fralin Biomedical Research Institute, sheds new light on this notion, revealing that the virus itself creates potentially dangerous conditions in the heart before inflammation sets in.
The discovery, now online and set to appear in the March 29 issue of Circulation Research, suggests completely new directions to diagnose and treat viral infections affecting the heart.
Given the high incidence of viral-related myocarditis leading to sudden cardiac death, the insight is crucial. Up to 42% of sudden cardiac deaths in young adults are attributed to myocarditis, and of these cases viral infection is the leading cause.
“From a clinical perspective, our understanding of viral infection of the heart has focused on inflammation, causing problems with the rate or rhythm of the heartbeat,” Smyth said. “But we have found an acute stage when the virus first infects the heart and before the body’s immune response causes inflammation. So even before the tissue is inflamed, the heart is being set up for arrhythmia.”
To make this discovery, researchers focused on adenovirus, a common culprit in cardiac infection and myocarditis, using Mouse Adenovirus Type-3 to replicate the human infection process.
They found that early in the infection, the virus disrupts critical components of the heart’s communication and electrical systems.
As a result, even before symptoms appear, the adenoviral infection creates conditions that disrupt the heart’s gap junctions and ion channels, according to virologist Rachel Padget, the study’s first author who worked in the Smyth lab while completing a doctoral degree from the Virginia Tech Translational Biology, Medicine, and Health graduate program.
Gap junctions are like tiny tunnels between heart cells that allow them to communicate, and ion channels are like gates in the cell membranes that help maintain the right balance of ions needed for the heart to generate normal patterns of electrical activity that allow it to beat properly.
When adenoviral infection disturbs these communication bridges and gatekeepers, it creates a situation where the heart might develop irregular patterns of electrical activity called arrhythmias affecting its mechanical beating and blood pumping capacity, and that can lead to sudden cardiac problems, especially in people with active infections.
Now, by targeting specific heart changes induced by viral infections at the molecular level, researchers aim to reduce the risk of cardiac issues in people grappling with viral illnesses.
“Individuals who have acute infections can look normal by MRI and echocardiography, but when we delved into the molecular level, we saw that something very dangerous could occur,” Smyth said. “In terms of diagnostics, we can now work with our colleagues here to start looking ways to analyse blood for a biomarker of the more serious problem. People get cardiac infections all the time and they recover. But can we identify what’s different about individuals that are at a higher risk to have the arrhythmia, possibly through a simple blood test in the doctor’s office.”
Cells with nuclei in blue, energy factories in green and the actin cytoskeleton in red. Credit: NIH
A new discovery, which was published in Nature Cell Biology, reveals how genetic material can escape mitochondria, prompting the body to launch a damaging immune response, setting off diseases such as lupus and rheumatoid arthritis. By developing therapies to target this process, doctors may one day be able to stop the harmful inflammation and prevent the toll it takes on our bodies.
“When mitochondria don’t correctly replicate their genetic material, they try to eliminate it. However, if this is happening too often and the cell can’t dispose of all of it, it can cause inflammation, and too much inflammation can lead to disease, including autoimmune and chronic diseases,” said researcher Laura E. Newman, PhD, of the University of Virginia School of Medicine. “Now that we are beginning to understand how this inflammation starts, we might be able to prevent this process, with the ultimate goal of limiting inflammation and treating disease.”
Powering inflammation
Mitochondria have their own set of genetic material, separate from the DNA that serves as the operating instructions for our cells. Scientists have known that this mitochondrial DNA, known as mtDNA, can escape into our cells and cause inflammation. But exactly what caused this has been a mystery until now.
“We knew that mtDNA was escaping mitochondria, but how was still unclear,” said Gerald Shadel, PhD, director of the San Diego-Nathan Shock Center of Excellence in the Basic Biology of Aging at the Salk Institute. “Using imaging and cell biology approaches, we’re able to trace the steps of the pathway for moving mtDNA out of the mitochondria, which we can now try to target with therapeutic interventions to hopefully prevent the resulting inflammation.”
Shadel and Newman, then a postdoctoral researcher in Shadel’s lab, and their collaborators used sophisticated imaging techniques to determine what was happening inside the leaky mitochondria. They found that the leak was triggered by a malfunction in mtDNA replication. This caused the accumulation of protein masses caused nucleoids.
To try to fix this problem, the cell containing the faulty mitochondrion begins to export the excess nucleoids to its cellular trash bins. But the trash bins, called endosomes, can become overwhelmed by the volume of debris, the scientists found. These overburdened endosomes respond by releasing mtDNA into the cell — in short, the trash can overflows.
“We had a huge breakthrough when we saw that mtDNA was inside of a mysterious membrane structure once it left mitochondria. After assembling all of the puzzle pieces, we realised that structure was an endosome,” Newman said. “That discovery eventually led us to the realisation that the mtDNA was being disposed of and, in the process, some of it was leaking out.”
The cell responds to this hazardous waste spill by flagging the nucleoids as foreign DNA, like a virus, and launches an immune response that results in harmful inflammation, the scientists determined.
“Using our cutting-edge imaging tools for probing mitochondria dynamics and mtDNA release, we have discovered an entirely novel release mechanism for mtDNA,” said researcher Uri Manor, PhD, former director of the Waitt Advanced Biophotonics Core at Salk and current assistant professor at UC San Diego. “There are so many follow-up questions we cannot wait to ask, like how other interactions between organelles control innate immune pathways, how different cell types release mtDNA, and how we can target this new pathway to reduce inflammation during disease and aging.”
Newman will continue to seek these answers in her new role at the UVA School of Medicine’s Department of Cell Biology. “We want to understand the physiological and disease contexts where this process can become activated,” she said. “For example, many viruses attack mitochondria during infection, so we will be testing whether mitochondria purposely use this pathway to sound the alarm against invading viruses, and whether over-reliance on this pathway to fight off infection can later trigger chronic diseases.”
