In a study published in the International Journal of Gynecology & Obstetrics, UK researchers have uncovered an association between the rate of eclampsia and the number of deaths caused by indoor household pollution, mostly from cooking and heating fires.
More commonly seen in low- and middle-income countries commonly using solid fuels, such as wood and charcoal, indoor household pollution has been proven to increase the risk of adverse birth outcomes, including placental hypoxia.
The researchers evaluated more than 2690 cases of eclampsia in Ethiopia, Haiti, India, Malawi, Sierra Leone, Uganda, Zambia and Zimbabwe, and found a significant correlation between deaths due to indoor household pollution and eclampsia rates – and the correlation was even more prominent when eclampsia occurred at home.
King’s College London’s Professor Andrew Shennan, one of the lead authors on the paper, said the findings demonstrate how air pollution can impact vulnerable populations the most.
“In-house cooking and household pollution may increase the risk of seizures. We believe that less oxygen will get to the mother’s brain, and this may trigger a fit in women who already have pre-eclampsia” he said.
“We are lucky to have such a large dataset of women with eclampsia, as it only occurs in 1% of women with pre-eclampsia. This has allowed us to uncover this new finding.
“This could help explain observed inequalities in maternal healthcare in low- and middle-income countries.”
In a previous study by King’s College London, scientists found that 94% of maternal deaths occur in low- and middle-income countries, with 22% due to hypertensive disorders like eclampsia.
Professor Shennan added: “Knowing why women have these severe outcomes allows us to reduce the risk of eclampsia and work out how to save lives.
“We have large programmes of work in India, Sierra Leone and Zambia where many women have complications related to high blood pressure. Our current research is aimed at identifying the women at risk but now we are looking at ways to reduce risk, including earlier delivery. This data will help us to give advice about avoiding risk at home.”
The researchers next plan to explore whether climate change increases the prevalence of pre-eclampsia or increases the morbidity from serious manifestations such as eclampsia.
The national Department of Health (DOH) has managed to secure a significant reduction in prices for antiretroviral medicines that treat HIV, with the price of the regimen that is prescribed to most new patients (tenofovir/lamivudine/dolutegravir – TLD) dropping over 30%, from R99 to R68. By comparison the regimen costs well over R250 in the private sector.
TLD is recommended by the World Health Organisation as the preferred first-line regimen for adults living with HIV.
Currently over 4 million South Africans are using this regimen, according to statistics from the DOH. There are about over 5.5 million people receiving treatment for HIV, and 8 million people living with the virus in this country.
Prices of ABC/3TC, commonly used to treat children with HIV, also fell with the DOH’s new contract.
Khadija Jamaloodien, director of the Affordable Medicines Directorate in the DOH, told GroundUp that South Africa is the biggest buyer of ARVs in the world. She said because of the sheer number of people needing ARVs, the department was able to bring the price down.
“Our volumes are just so huge that it makes it more efficient for manufacturers to be able to supply at reasonable prices,” said Jamaloodien.
She said another reason the department was able to reduce the price was that the manufacturers were applying for a three-year contract with “a certainty of demand”. She said constant communication with manufacturers about changes in demand also helped. If demand is likely to be reduced, the department would inform manufacturers who then would not “sit with stock that they are going to have to write off”.
The contract, which is already being executed, was awarded from July 2022 and ends in June 2025.
Jamaloodien said lower prices meant that the department could serve more patients and provide more medicines within the same budget envelope. (ARVs are provided free to public sector patients.)
Juliet Houghton, CEO of the Southern African HIV Clinicians Society (SAHCS), praised the DOH’s efforts to secure the ARVs so cheaply. She said a “healthy” degree of competition between manufacturers also helped drive prices down.
Houghton added that the reduction in prices “offers an opportunity to reinvest some of the savings into more expensive, particularly prevention drugs, that are coming”.
“As a country, we don’t want to just keep treating more and more people with HIV, we actually want to prevent it,” said Houghton. She said that the remaining budget could also be invested in prevention injectables, which might be more expensive.
Jamaloodien said that the injectable pre-exposure prophylaxis (PrEP) medicines are not yet registered with South African Health Products Regulatory Authority (SAHPRA). These help prevent sexually active people from contracting HIV. She said after the medicines are registered, they will have to look at whether they are affordable.
Francois Venter, executive director of Ezintsha at Wits, also praised the DOH’s “excellent work in securing these price reductions”.
“We also need the department to start using these processes better to secure similar world-class treatments for other common diseases – including diabetes, cancer, obesity, and TB,” he said.
By taking advantage of a phenomenon that is usually an engineering headache, MIT researchers have designed a liquid metal to safely disintegrate metal medical implants and drug depots when they are not needed anymore.
In their work published in Advanced Materials, the researchers showed that aluminium biomedical devices can be disintegrated by exposing them to a liquid metal known as eutectic gallium-indium (EGaIn). In practice, this might work by painting the liquid onto staples used to hold skin together, for example, or by administering EGaIn microparticles to patients.
According to the researchers, disintegrating metal devices in this way could eliminate the need for surgical or endoscopic removal procedures.
“It’s a really dramatic phenomenon that can be applied to several settings,” says senior author Giovanni Traverso, assistant professor of mechanical engineering at MIT and a gastroenterologist at Brigham and Women’s Hospital. “What this enables, potentially, is the ability to have systems that don’t require an intervention such as an endoscopy or surgical procedure for removal of devices.”
Breaking down metals
For several years, Traverso’s lab has been working on ingestible devices that could remain in the digestive tract for days or weeks, releasing drugs on a specific schedule.
Most of those devices are made from polymers, but recently the researchers have been exploring the possibility of using metals, which are stronger and more durable. However, one of the challenges of delivering metal devices is finding a way to remove them once they’re no longer needed.
Right now, removing the staples can actually induce more tissue damage
Vivian Feig, MIT POSTDOC & First Author
To create devices that could be broken down on demand inside the body, the MIT turned to liquid metal embrittlement. This process has been well-studied as a source of failure in metal structures, including those made from zinc and stainless steel. It is why metal liquids such as mercury are not allowed on aircraft.
“It’s known that certain combinations of liquid metals can actually get into the grain boundaries of solid metals and cause them to dramatically weaken and fail,” says first author Vivian Feig, an MIT postdoc. “We wanted to see if we could harness that known failure mechanism in a productive way to build these biomedical devices.”
One room-temperature liquid metal that can induce embrittlement is gallium. For this study, the researchers used eutectic gallium-indium, an alloy of gallium that scientists have explored for a variety of applications in biomedicine as well as energy and flexible electronics.
For the devices themselves, the researchers chose to use aluminium, which is known to be susceptible to embrittlement when exposed to gallium.
Gallium weakens solid metals such as aluminium in two ways. First, it can diffuse through the grain boundaries of the metal – border lines between the crystals that make up the metal – causing pieces of the metal to break off. The MIT team showed that they could harness this phenomenon by designing metals with different types of grain structures, allowing the metals to break into small pieces or to fracture at a given point.
Gallium also prevents aluminium from forming a protective oxide layer on its surface, which increases the metal’s exposure to water and enhances its degradation.
The MIT team showed that after they painted gallium-indium onto aluminium devices, the metals would disintegrate within minutes. The researchers also created nanoparticles and microparticles of gallium-indium and showed that these particles, suspended in fluid, could also break down aluminium structures.
On-demand disintegration
While the researchers began this effort as a way to create devices that could be broken down in the gastrointestinal tract, they soon realised that it could also be applied to other biomedical devices such as staples and stents.
To demonstrate GI applications, the researchers designed a star-shaped device, with arms attached to a central elastomer by a hollow aluminium tube. Drugs can be carried in the arms, and the shape of the device helps it be retained in the GI tract for an extended period of time. In a study in animals, the researchers showed that this kind of device could be broken down in the GI tract upon treatment with gallium-indium.
The researchers then created aluminium staples and showed that they could be used to hold tissue together, then dissolved with a coating of gallium-indium.
“Right now, removing the staples can actually induce more tissue damage,” Feig says. “We showed that with our gallium formulation we can just paint it on the staples and get them to disintegrate on-demand instead.”
The researchers also showed that an aluminium stent they designed could be implanted in oesophageal tissue, then broken down by gallium-indium.
Currently, oesophageal stents are either left in the body permanently or endoscopically removed when no longer needed. Such stents are often made from metals such as nitinol, an alloy of nickel and titanium. The researchers are now working to see if they could create dissolvable devices from nitinol and other metals.
“An exciting thing to explore from a materials science perspective is: Can we take other metals that are more commonly used in the clinic and modify them so that they can become actively triggerable as well?” Feig says.
Initial toxicity studies in rodents showed that gallium-indium was non-toxic even at high doses. However, more study would be needed to ensure it would be safe to administer to patients, the researchers say.
A new study using a mouse model suggests that a short-term exposure to a high-fat diet may be linked to pain sensations, such as from a light touch, even without a prior injury or a pre-existing condition like obesity or diabetes. This finding may help in part explain the severity of the opioid crisis.
The study, published in Scientific Reports, compared the effects of eight weeks of different diets on two cohorts of mice. One group received normal chow, while the other was fed a high-fat diet in a way that did not precipitate the development of obesity or high blood sugar, both of which are conditions that can result in diabetic neuropathy and other types of pain.
The researchers found that the high-fat diet induced hyperalgesic priming – a neurological change that represents the transition from acute to chronic pain – and allodynia, which is pain resulting from stimuli that do not normally provoke pain.
“This study indicates you don’t need obesity to trigger pain; you don’t need diabetes; you don’t need a pathology or injury at all,” said Dr Michael Burton, assistant professor of neuroscience and corresponding author of the article. “Eating a high-fat diet for a short period of time is enough – a diet similar to what almost all of us in the US eat at some point.”
The study also compared obese, diabetic mice with those that just experienced dietary changes.
“It became clear, surprisingly, that you don’t need an underlying pathology or obesity. You just needed the diet,” Burton said. “This is the first study to demonstrate the influential role of a short exposure to a high-fat diet to allodynia or chronic pain.”
Diet itself caused markers of neuronal injury.
Western diets are rich in fats – in particular saturated fats, which have proved to be responsible for an epidemic of obesity, diabetes and associated conditions. Individuals who consume high amounts of saturated fats – like butter, cheese and red meat – have high amounts of free fatty acids circulating in their bloodstream that in turn induce systemic inflammation.
Recently, scientists have shown that these high-fat diets also increase existing mechanical pain sensitivity in the absence of obesity, and that they can also aggravate pre-existing conditions or imped injury recovery. To date, no studies have explained how high-fat diets alone can be a sensitising factor in inducing pain from nonpainful stimuli, such as a light touch on the skin, Burton said.
“We’ve seen in the past that, in models of diabetes or obesity, only a subsection of the people or animals experience allodynia, and if they do, it varies across a spectrum, and it isn’t clear why,” Burton said. “We hypothesized that there had to be other precipitating factors.”
The researchers examined blood levels of fatty acids in the mice. They found that a fatty acid called palmitic acid, the most common saturated fatty acid in animals, binds to a particular receptor on nerve cells, a process that results in inflammation and mimics injury to the neurons.
“The metabolites from the diet are causing inflammation before we see pathology develop,” Burton said. “Diet itself caused markers of neuronal injury.
The mechanism behind this transition is important because it is the presence of chronic pain – from whatever source – that is fuelling the opioid epidemic
“Now that we see that it’s the sensory neurons that are affected, how is it happening? We discovered that if you take away the receptor that the palmitic acid binds to, you don’t see that sensitising effect on those neurons. That suggests there’s a way to block it pharmacologically.”
Burton said the next step will be to focus on the neurons themselves – how they are activated and how injuries to them can be reversed. It is part of a larger effort to understand better the transition from acute to chronic pain.
“The mechanism behind this transition is important because it is the presence of chronic pain – from whatever source – that is fuelling the opioid epidemic,” he said. “If we figure out a way to prevent that transition from acute to chronic, it could do a lot of good.”
Burton said he hopes his research encourages health care professionals to consider the role diet plays in influencing pain.
“The biggest reason we do research like this is because we want to understand our physiology completely,” he said. “Now, when a patient goes to a clinician, they treat a symptom, based off of an underlying disease or condition. Maybe we need to pay more attention to how the patient got there: Does the patient have diabetes-induced or obesity-induced inflammation; has a terrible diet sensitised them to pain more than they realized? That would be a paradigm shift.”
Cannabis use may negatively impact outcomes in peripheral artery bypass (PAB) surgery, suggests a study published in Annals of Vascular Surgery.
Researchers analysed more than 11 000 available cases to review patient cannabis use and postoperative outcomes for lower extremity bypass after 30 days and one year. The minimally invasive PAB procedure uses a vein or synthetic to tube to divert blood around a narrowed or blocked artery in a leg.
Results reveal that patients who used cannabis prior to lower extremity bypass had decreased patency, meaning the graft had a higher chance of becoming blocked or occluded, and were 1.25 times more likely to require amputation one year after surgery. Cannabis users were also 1.56 times more likely to use opioids after discharge.
“The findings show a need for screening for cannabis use and open conversations between patients and clinicians to help inform preoperative risk assessment and decision-making for lower extremity bypass,” said senior author Peter Henke, MD, FACS, FAHA
“While its exact mechanisms are unclear, cannabis and its active compounds play a role in platelet function and microcirculation that may lead to decreased rates of limb salvage after lower extremity bypass,” Henke said.
Around 43% of individuals in the United States and Canada have used cannabis. Previous studies suggest cannabis use has effects on the cardiovascular system, including increased risk of heart attack and stroke. The study did not find any association with stroke or heart attack after lower extremity bypass.
While future study is needed to further understand cannabis’ full effect on outcomes, researchers note, the findings will help clinicians counsel patients who are undergoing vascular surgery.
“While past studies on the effects of cannabis use on pain response suggested an increase in pain tolerance after smoking cannabis, our studies and other contemporary findings show the opposite,” said Drew Braet, M.D., first author and integrated vascular surgery resident at U-M Health. “Given the increase in cannabis use and abuse in conjunction with the opioid epidemic, the results suggest a need for a better understanding of pain management for cannabis users who are having vascular surgery.”
