In the first study of its kind, University of South Australia researchers report that people who reported trouble sleeping were on average more likely to have indicators of poor cardiometabolic health – inflammatory markers, cholesterol and body weight – which can contribute to type 2 diabetes. The study was published in The Science of Diabetes Self-Management and Care.
Type 2 diabetes affects more than 422 million people around the globe.
As the Christmas season starts to ramp up, the UniSA researchers are reminding people to prioritise a good night’s sleep as new research shows that a troubled sleep may be associated with risk factors for type 2 diabetes.
UniSA researcher Dr Lisa Matricciani says different aspects of sleep are associated with risk factors for diabetes.
“Everyone knows that sleep is important. But when we think about sleep, we mainly focus on how many hours of sleep we get, when we should also be looking at our sleep experience as a whole,” Dr Matricciani says.
“How soundly we sleep, when we go to bed and get up, and how regular our sleep habits are, may be just as important as sleep duration.”
“In this study, we examined the association of different aspects of sleep, and risk factors for diabetes, and found a connection between those who had troubled sleep and those who were at risk of type 2 diabetes.”
The study assessed more than 1000 Australian adults* with a median age of 44.8 years. Researchers examined a range of sleep characteristics: self-report trouble sleeping, duration, timing, efficiency, and day-to-day sleep length variability.
“People who reported having trouble sleeping were also more likely to have a higher body mass index, as well as blood markers of cholesterol and inflammation,” Dr Matricciani says.
“When it comes down to the crunch, we know we must prioritise our sleep to help stay in good health. More research is needed, but as this study shows, it’s important to think about sleep as a whole, not just as one aspect.”
Notes
*Most participants (87%) were mothers.
48% of all participants reported that they never had troubled sleep.
In 2020, pharmaceutical company ViiV Healthcare announced that a bimonthly injection of its new drug, cabotegravir, prevents HIV infection. More than two years later, the drug is still unaffordable in countries where HIV is highly prevalent.
Local medicines manufacturer Aspen Pharmacare says that licences should be given to African producers so that cabotegravir can be made more affordable and accessible.
Cabotegravir can be used to prevent HIV infection. This is known as Pre-Exposure Prophylaxis, or PreP. Currently, PrEP is only available in pill form and has to be taken daily. A bimonthly injection is an appealing alternative that, if made widely available, can make a big dent in the HIV infection rate.
Globally, 1.5-million people are infected with HIV and about 650,000 people die of AIDS every year. UNAIDS’s target of reducing annual infections to fewer than 500,000 by 2020 was not reached. It is widely accepted among experts that prevention as well as treatment is necessary to end the epidemic.
Although the World Health Organisation has recommended cabotegravir for PrEP, it is unaffordable, especially in developing countries where HIV is most prevalent. The Clinton Health Access Initiative (CHAI) has estimated that cabotegravir could be manufactured for just over $65 (R1100) a year.
According to The Guardian, ViiV’s not-for-profit price for cabotegravir is estimated to be $240-$270 (R4,059-R4,567) for a full year’s supply for one patient.
But in the United States, a full year’s supply for one person of cabotegravir is sold for more than $22,000 (R370,000). In the UK a year’s supply is $9,275.
In comparison, oral PrEP costs about R686 for a full year’s supply for one patient in South Africa. Cabotegravir is not yet approved by the South African Health Products Regulatory Authority.
Stavros Nicolaou, group senior executive strategic trade at Aspen Pharmacare, says that there is local capability to manufacture cabotegravir but licences have not yet been granted. The company invested heavily in sterile equipment, needed to produce injections, during the Covid-19 pandemic. This can be used to produce cabotegravir.
Aspen is the biggest producer of antiretrovirals (ARVs) in Africa. Nicolaou says that giving licences to African producers is crucial to ensuring the equitable supply of medication.
ViiV has committed to allowing generic versions of the drug to be manufactured but has said that the process is complicated. Cabotegravir is currently only manufactured at one site in the UK.
In July, activists interrupted presentations during the AIDS 2022 conference in Montreal, calling on ViiV to lower the price of cabotegravir. Doctors Without Borders (Médecins Sans Frontières) has urged ViiV to make the drug available in high-prevalence countries and to be more transparent about its pricing and manufacturing process.
ViiV has come to an agreement with the Medicines Patent Pool (MPP), a nonprofit organisation that will facilitate the process of awarding licences to manufacturers.
But Dr Andrew Hill from the Department of Pharmacology at the University of Liverpool says that the agreement is highly restrictive.
Hill says that many countries have been excluded from the list, particularly those in South America and Asia, including those with high HIV infection rates.
He says that most of the world’s population could be reached if cabotegravir was made available at the CHAI price of $65 (R1100) per patient per year. That it is not yet widely available is a “failure of public health”, he told GroundUp.
In South Africa, where just under 14% of the population has HIV, the announcement of cabotegravir two years ago was widely celebrated among clinicians.
The researchers we spoke to suggest that the uptake of cabotegravir would be higher than that of PreP tablets and so it would be more effective. Most new infections in Sub-Saharan Africa are among women and adolescent girls. Cabotegravir offers them a discreet alternative and one that doesn’t require daily adherence.
“It’s very frustrating,” says Juliet Houghton, CEO of the Southern African HIV Clinicians Society. Houghton says that if cabotegravir can be rolled out in pharmacies across the country, with pharmacists allowed to administer it, it will greatly increase the uptake of PrEP and reduce infections.
“We can’t just keep treating people for HIV,” Houghton says. “Prevention has to be the way forward.”
“We need to look at PreP closer to the way we look at contraception,” says Andy Gray, senior lecturer in Pharmacology at the University of KwaZulu-Natal. Offering more choices that fit into a variety of lifestyles is likely to improve the uptake of PrEP, he says.
Dr Yogan Pillay, country director for CHAI, says that governments and civil organisations need to pressure ViiV and MPP to increase the availability of cabotegravir.
“That 82% of the 250 000 adolescent girls and women that acquired HIV in 2021 are in Sub-Saharan Africa makes it imperative that cabotegravir is made available at an affordable price as soon as possible,” Pillay says.
“We need this drug, we need it now, and we need truckloads,” says Professor Francois Venter, executive director of Ezintsha at Wits. “It works very well. It is safe. And while we still have to figure out how to use it best, we can’t do that with nothing in hand.”
A spokesperson for ViiV Healthcare told GroundUp: “We believe cabotegravir long-acting (LA) for PrEP has the potential to change the shape of the HIV epidemic and we are ambitious for the impact we can have together with global health partners to bring this medicine to those who need it.”
ViiV says that at first, three generic manufacturers will be selected by MPP.
“Enabling up to three generics in the first instance allows for competition but avoids a fractured market with too many manufacturers and a risk of there not being enough demand to sustain the long-term manufacturing commitments to be made by licensees,” ViiV said.
ViiV also said they are working with various partners to ensure that Cabotogrevir is accessible to countries in Sub-Sarahan Africa.
“We know that affordability is a real challenge in these countries, and we are working with our partners to look at affordable pricing, demand and innovative funding mechanisms to help enable access for people who could benefit from PrEP,” ViiV said.
ViiV says that CHAI’s price estimation is unrealistic because of the complexity of the manufacturing process.
People can achieve some pain relief by rubbing or pressing a part of their body associated with the pain. Observing for the first time how this phenomenon plays out in the brains of mice, MIT scientists suggest that pain-responsive cells in the brain quiet down when these neurons also receive touch inputs.
The team’s discovery, reported in the journal Science Advances, offers researchers a deeper understanding of the complicated relationship between pain and touch and could offer some insights into chronic pain in humans. “We’re interested in this because it’s a common human experience,” says investigator Fan Wang. “When some part of your body hurts, you rub it, right? We know touch can alleviate pain in this way.” But, she says, the phenomenon has been very difficult for neuroscientists to study.
Modelling pain relief
The spinal cord may be where touch-mediated pain relief begins, as prior studies have found pain-responsive neurons that reduce activity in response to touch. But there have been hints that the brain was involved, too. Wang says this aspect of the response has been largely unexplored, because it can be hard to monitor the brain’s response to painful stimuli amidst all the other neural activity happening there. particularly when an animal moves.
So while her team knew that mice respond to a potentially painful stimulus on the cheek by wiping their faces with their paws, they couldn’t follow the specific pain response in the animals’ brains to see if that rubbing helped settle it down. “If you look at the brain when an animal is rubbing the face, movement and touch signals completely overwhelm any possible pain signal,” Wang explains.
She and her colleagues have found a way around this obstacle. Instead of studying the effects of face-rubbing, they have focused their attention on a subtler form of touch: the gentle vibrations produced by the movement of the animals’ whiskers. Mice use their whiskers to explore, moving them back and forth in a rhythmic motion known as whisking to feel out their environment. This motion activates touch receptors in the face and sends information to the brain in the form of vibrotactile signals. The human brain receives the same kind of touch signals when a person shakes their hand as they pull it back from a painfully hot pan — another way we seek touch-mediate pain relief.
Whisking away pain
Wang and her colleagues found that this whisker movement alters the way mice respond to bothersome heat or a poke on the face – both of which usually lead to face rubbing. “When the unpleasant stimuli were applied in the presence of their self-generated vibrotactile whisking … they respond much less,” she says. Sometimes, she says, whisking animals entirely ignore these painful stimuli.
In the brain’s somatosensory cortex, where touch and pain signals are processed, the team found signalling changes that seem to underlie this effect. “The cells that preferentially respond to heat and poking are less frequently activated when the mice are whisking,” Wang says. “They’re less likely to show responses to painful stimuli.” Even when whisking animals did rub their faces in response to painful stimuli, the team found that neurons in the brain took longer to adopt the firing patterns associated with that rubbing movement. “When there is a pain stimulation, usually the trajectory the population dynamics quickly moved to wiping. But if you already have whisking, that takes much longer,” Wang says.
Wang notes that even in the fraction of a second before provoked mice begin rubbing their faces, when the animals are relatively still, it can be difficult to sort out which brain signals are related to perceiving heat and poking and which are involved in whisker movement. Her team developed computational tools to disentangle these, and are hoping other neuroscientists will use the new algorithms to make sense of their own data.
Whisking’s effects on pain signalling seem to depend on dedicated touch-processing circuitry that sends tactile information to the somatosensory cortex from the ventral posterior thalamus. When that pathway was blocked, whisking no longer dampened the animals’ response to painful stimuli. Now, Wang says, she and her team are eager to learn how this circuitry works with other parts of the brain to modulate the perception and response to painful stimuli.
The new findings might shed light on a condition called thalamic pain syndrome, a chronic pain disorder that can develop in patients after a stroke that affects the brain’s thalamus, says Wang. “Such strokes may impair the functions of thalamic circuits that normally relay pure touch signals and dampen painful signals to the cortex.”
A novel technology described in the journal Nanoscale enables targeted destruction of cancerous tumours, via a combination of ultrasound and the injection of nanobubbles into the bloodstream. Unlike invasive treatment methods or the injection of microbubbles into the tumour itself, this latest technology enables the destruction of the tumour in a non-invasive manner.
Dr Tali Ilovitsh at Tel Aviv University said: “Our new technology makes it possible, in a relatively simple way, to inject nanobubbles into the bloodstream, which then congregate around the cancerous tumour. After that, using a low-frequency ultrasound, we explode the nanobubbles, and thereby the tumour.”
At present, the usual cancer treatment is surgical removal of the tumour, in combination with complementary treatments such as chemotherapy and immunotherapy.
Therapeutic ultrasound to destroy the cancerous tumour is a non-invasive alternative to surgery, a method which comes with advantages and disadvantages. On the one hand, it allows for localised and focused treatment; the use of high-intensity ultrasound can produce thermal or mechanical effects by delivering powerful acoustic energy to a focal point with high spatial-temporal precision. This method has been used to effectively treat solid tumours deep within in the body. Moreover, it makes it possible to treat patients who are unfit for tumour resection surgery. The disadvantage is that the heat and high intensity of the ultrasound waves could cause damage to neighbouring healthy tissues.
Reducing off-target damage
In the current study, Dr Ilovitsh and her team sought to overcome this problem. In the experiment, which used an animal model, the researchers were able to destroy the tumour by injecting nanobubbles into the bloodstream (as opposed to what has been until now, which is the local injection of microbubbles into the tumour itself), in combination with low-frequency ultrasound waves, with minimal off-target effects.
“The combination of nanobubbles and low frequency ultrasound waves provides a more specific targeting of the area of the tumour, and reduces off-target toxicity,” explains Dr Ilovitsh.
“Applying the low frequency to the nanobubbles causes their extreme swelling and explosion, even at low pressures. This makes it possible to perform the mechanical destruction of the tumours at low-pressure thresholds.”
“Our method has the advantages of ultrasound, in that it is safe, cost-effective, and clinically available, and in addition, the use of nanobubbles facilitates the targeting of tumours because they can be observed with the help of ultrasound imaging.”
Dr Ilovitsh adds that the use of low-frequency ultrasound also increases the depth of penetration, minimises distortion and attenuation, and enlarges the focal point. “This can help in the treatment of tumours that are located deep with the body, and in addition facilitate the treatment of larger tumour volumes. The experiment was conducted in a breast cancer tumour lab model, but it is likely that the treatment will also be effective with other types of tumours, and in the future, also in humans.”
