During childhood, about one in 20 people go through a period of stuttering. Until the latter half of the 20th century, stuttering was believed to be a psychological problem stemming from lack of effort or from trauma.
Nowadays, neuroimaging techniques are leading to a much better understanding of brain function during speech and how stuttering arises. Frank Guenther, from Boston University, reported findings from a new study at the 181st Meeting of the Acoustical Society of America.
Guenther gives the example of speech being a jukebox that plays CDs. The jukebox has two circuits: one that chooses a CD and one that plays the CD.
In the brain, this corresponds to one circuit initiating the desired speech in the basal ganglia, while another circuit coordinates the muscles needed to generate the speech. Stuttering stems from the initiation of speech, so only the first of the two circuits is impaired.
“In stuttering, the CDs themselves are fine, but the mechanism for choosing them is impaired,” said Guenther.
This theory is in agreement with behavioural observations of stuttering: people will often speak words fluently later in a sentence, even if those same words cause stuttering at the start of a sentence.
Guenther and his team created computational models of how the speech initiation circuit performs in a non-stuttering individual. Since Parkinson’s disease also affects the initiation circuit, they can compare these models directly to data taken from the basal ganglia during deep brain stimulation surgery in patients with the disease.
“This gives us a fighting chance of finding the specific problems underlying stuttering and addressing them with highly targeted drugs or technological treatments that have minimal unwanted side effects,” said Guenther.
A large study has shown that apolipoproteins apoB and apoA-1 together provide early and reliable cardiovascular risk information as well as levels of low-density lipoprotein (LDL) cholesterol. The researchers advocate introducing new guidelines for detecting cardiac risk and say the results, published in PLOS Medicine, may pave the way for early treatment, which could help lower morbidity and mortality rates.
Cardiovascular disease is the most common cause of death globally and includes a wide range of conditions, such as stroke and myocardial infarction with atherosclerosis in different organs of the body. In many cases the disease can be prevented and arrested with lifestyle changes and lipid-lowering treatments using statins and other methods.
The cardiac risk assessment usually uses reference values for the LDL cholesterol. Other types of fat particles can also be measured along with apolipoproteins, which transport cholesterol in the blood. International guidelines for cardiovascular disease recommend using apolipoprotein apoB, which transports LDL cholesterol, as an alternative risk marker for people with type 2 diabetes, overweight and very high levels of blood lipids.
Recent research has, however, indicated the importance of also factoring in the apolipoprotein apoA-1, which transports the protective and anti-inflammatory HDL cholesterol. Calculating the apoB/apoA-1 ratio gives a risk quotient reflecting the balance between the fat particles that expedite atherosclerosis and the “good” protective apoA-1 particles that arrest the process.
In this present study, the researchers have analysed the link between cardiovascular disease and apoB/apoA-1 values in more than 137 000 Swedish adults between the ages of 25 and 84. The individuals were followed for 30 years, during which time 22 000 suffered some form of cardiovascular event. The analysis methods are simple, inexpensive and safe, and do not require pre-test fasting, as is the case with LDL and non-HDL tests. Basing their study on a large database, the researchers linked the laboratory analyses to several clinical diagnosis registers.
“The results show that the higher the apoB/apoA-1 value, the greater the risk of myocardial infarction, stroke and need for coronary surgery,” says Göran Walldius, senior author and professor emeritus at the Institute of Environmental Medicine, Unit of Epidemiology, Karolinska Institutet. “The study also showed that the risk was amplified in the presence of low protective levels of apoA-1.”
Individuals with the highest apoB/apoA-1 values had a 70% higher risk of severe cardiovascular disease and almost triple the risk of non-fatal myocardial infarction compared with those with the lowest apoB/apoA-1 values. Individuals with the highest risk quotient were also more affected by severe cardiovascular diseases many years earlier than individuals with the lowest apoB/apoA-1 values.
The relationship was observed in both men and women and the elevated levels could be detected as early as 20 years before the onset of cardiovascular disease.
“Early preventive treatment and information about cardiovascular risk is, of course, important in enabling individuals to manage their risk situation,” Walldius says. “Early treatment can also reduce the cost burden on the public health services.”
Taken together, the results suggest that the apoB/apoA-1 ratio is a better marker for identifying at-risk individuals for cardiovascular disease compared to the apoB method alone.
“It should be possible to introduce cut-values for apoB, apoA-1 and the apoB/apoA-1 ratio into new guidelines as a complement to current guidance on the detection and treatment of dyslipidaemia,” said Walldius.
A new analysis published in PLOS ONE highlights the worldwide prevalence of HIV among transgender people, demonstrating the need for continued prevention efforts.
Transgender individuals have an increased risk of HIV infection, due to factors which are numerous, complex, and dynamic. Recent years have seen updates in HIV prevention measures and so it is important to update knowledge of HIV among transgender individuals in order to inform further prevention efforts.
Applying a statistical method called random-effects modeling, the researchers conducted a meta-analysis of all 98 peer-reviewed publications on HIV prevalence among transgender individuals that appeared between January 2000 and January 2019.
The researchers found that, during the study period, 19.9% (confidence interval [CI] 14.7–25.1%) of trans feminine individuals were HIV positive, as were 2.56% (CI 0.0–5.9%) of trans masculine individuals. Compared with other individuals aged 15 and over, trans feminine people were 66 times more likely (51.4– 84.4) to have HIV, and trans masculine people were 6.8 times more likely (3.6–13.1).
The authors note that their findings counter presumptions that trans masculine individuals are not at risk for HIV. Meanwhile, they found, prevalence varied in different geographic regions, with Africa and Latin America appearing to be more impacted.
Overall, these findings reaffirm that transgender individuals face a disproportionate burden of HIV. The researchers call for increased efforts to meet the unique HIV prevention and care needs of this population.
Continued monitoring will require more data and research, especially to determine how prevalence is influenced by pre-exposure prophylaxis (PrEP)—medications that prevent HIV infection. Such research will be especially important considering that the new study only included data up to 2019, and PrEP treatment has expanded since then.
A cloud of platelet factor 4 proteins interacting with the electrostatic surface of the Oxford vaccine, as seen through the computational microscope. Credit: Chun Kit Chan, Arizona State University
An international team of scientists believe they may have found a molecular mechanism behind the extremely rare blood clots linked to adenovirus vaccines.
Scientists led by a team from Arizona State University, Cardiff University and others worked with AstraZeneca to investigate vaccine-induced immune thrombotic thrombocytopenia (VITT), also known as thrombosis with thrombocytopenia syndrome (TTS), a life-threatening condition seen in a very small number of people after receiving the Oxford-AstraZeneca or Johnson & Johnson vaccines.
“The mechanism which results in this condition, termed vaccine-induced immune thrombotic thrombocytopenia (VITT), was unknown,” said Abhishek Singharoy, an Arizona State University scientist and corresponding author of the study who teamed up to lead an international effort to tease out the details.
Together, the team worked to solve the structural biology of the vaccine, and see the molecular details that may be at play, utilising state-of-the cryo-EM technology to analyse the AstraZeneca vaccine in minute detail. They sought to understand whether the ultra-rare side effect could be linked to the viral vector which is used in many vaccines, including those from Oxford/AstraZeneca and Johnson & Johnson.
Their findings suggest it is the viral vector – in this case, an adenovirus used to shuttle the coronavirus’ genetic material into cells – and the way it binds to platelet factor 4 (PF4) once injected that could be the potential mechanism.
In very rare cases, the scientists suggest, the viral vector may enter the bloodstream and bind to PF4, where the immune system then views this complex as foreign. They believe this misplaced immunity could result in the release of antibodies against PF4, which bind to and activate platelets, leading to clustering and blood clotting.
“It’s really critical to fully investigate the vector-host interactions of the vaccine at a mechanistic level,” said Singharoy. “This will assist in understanding both how the vaccine generates immunity, and how it may lead to any rare adverse events, such as VITT.”
Adenovirus expert Professor Alan Parker said: “VITT only happens in extremely rare cases because a chain of complex events needs to take place to trigger this ultra-rare side effect. Our data confirms PF4 can bind to adenoviruses, an important step in unravelling the mechanism underlying VITT. Establishing a mechanism could help to prevent and treat this disorder.”
“We hope our findings can be used to better understand the rare side effects of these new vaccines – and potentially to design new and improved vaccines to turn the tide on this global pandemic.”
The AstraZeneca and Johnson & Johnson vaccines both use an adenovirus to carry SARS-CoV-2 Spike proteins to trigger an immune response.
Since VITT was seen in both vaccines, scientists wondered whether the viral vector was involved. Additionally, neither the Moderna nor Pfizer vaccines, both mRNA vaccines, showed this effect.
Using cryo-EM technology to flash-freeze preparations of ChAdOx1, the adenovirus used in the AstraZeneca vaccine, they produce microscopic images of the vaccine components.
They were then able to view the viral capsid structure and other critical proteins that allow entry of the virus into the cell.
In particular, the team outlined the details for the structure and receptor of ChAdOx1, which is adapted from chimpanzee adenovirus Y25 – and how it interacts with PF4. They believe it is this specific interaction – and how it is then presented to the immune system – that could cuase the immune system to see it as foreign and release antibodies against this self-protein.
The research team also used computational models to show that one of the ways the two molecules tightly bind is via electrostatic interactions. The group showed that ChAdOx1 is mostly electronegative, attracting other positively charged molecules to its surface.
First author Dr Alexander Baker said: “We found that ChAdOx1 has a strong negative charge. This means the viral vector can act like a magnet and attract proteins with the opposite, positive charge, like PF4.” Baker is a member of ASU’s Biodesign Center for Applied Structural Discovery and an Honorary Research Fellow at Cardiff University School of Medicine.
“We then found that PF4 is just the right size and shape that when it gets close to ChAdOx1 it could bind in between the negatively charged parts of ChAdOx1’s surface, called hexons.”
The research team are hopeful that armed with a better understanding of what may be causing rare VITT they can provide further insights into how vaccines and other therapies, which rely on the same technology, might be altered in the development of the next generation vaccines and therapies.
“With a better understanding of the mechanism by which PF4 and adenoviruses interact there is an opportunity to engineer the shell of the vaccine, the capsid, to prevent this interaction with PF4. Modifying ChAdOx1 to reduce the negative charge may reduce the chance of causing thrombosis with thrombocytopenia syndrome,” said Baker.
The team likened it to the ‘two birds, one stone’ effect. The key contacts of individual amino acids that are essential to the capsid protein’s proteins interaction with PF4 can removed or substituted.
“The modification of the ChAdOx1 hexons to reduce their electronegativity may solve two problems simultaneously: reduce the propensity to cause VITT to even lower levels, and reduce the levels of pre-existing immunity, thus helping to maximize the opportunity to induce robust immune responses, said Singharoy.”
The Phoenix99 Bionic Eye. Credit: University of Sydney
A bionic eye under development has shown to be safe and stable for long-term implantation in a three-month animal study, paving the way towards human trials.
The Phoenix99 Bionic Eye, being developed by University of Sydney and UNSW, is an implantable system, designed to restore a form of vision to patients living with severe vision impairment and blindness caused by degenerative diseases, such as retinitis pigmentosa. The device consists of two main implants: a stimulator attached to the eye and a communication module positioned under the skin behind the ear.
Published in Biomaterials, the researchers used a sheep model to observe how the body responds and heals when implanted with the device, with the results allowing for further refinement of the surgical procedure. The biomedical research team is now confident the device could be trialled in human patients and have applied for ethical approval.
The Phoenix99 Bionic Eye works by stimulating the retina which, in healthy eyes, the cells in one of the layers turn incoming light into electrical messages. In some retinal diseases, the cells responsible for this crucial conversion degenerate, causing vision impairment. The system bypasses these malfunctioning cells by stimulating the remaining cells directly, effectively tricking the brain into believing that light was sensed.
“Importantly, we found the device has a very low impact on the neurons required to ‘trick’ the brain. There were no unexpected reactions from the tissue around the device and we expect it could safely remain in place for many years,” said Mr Samuel Eggenberger, a biomedical engineer who is completing his doctorate with Head of School of Biomedical Engineering Professor Gregg Suaning.
“Our team is thrilled by this extraordinary result, which gives us confidence to push on towards human trials of the device. We hope that through this technology, people living with profound vision loss from degenerative retinal disorders may be able to regain a useful sense of vision,” said Mr Eggenberger.
Professor Gregg Suaning said the positive results are a significant milestone for the Phoenix99 Bionic Eye.
“This breakthrough comes from combining decades of experience and technological breakthroughs in the field of implantable electronics,” said Prof Suaning.
A patient is implanted with the Phoenix99, and a stimulator is positioned on the eye and a communication module implanted behind the ear. A tiny camera attached to glasses captures the visual scene in front of the wearer, and the images are processed into a set of stimulation instructions which are sent wirelessly through to the communication module of the prosthesis.
The implant then transfers the instructions to the stimulation module, which delivers electrical impulses to the neurons of the retina. The electrical impulses, delivered in patterns matching the images recorded by the camera, trigger neurons which forward the messages to the brain, which interprets the signals as seeing the scene.
New research published in the Journal of Food and Medicine reports that daily prunes consumption protects bone health in men over 50. This study is the first of its kind to examine the beneficial prune effect on bones in men.
Some 2 million men are estimated to be battling osteoporosis and another 16.1 million men have osteopenia, or low bone mass. Despite these numbers, bone disease in men is often overlooked.
“We’ve already seen significant evidence that prunes have a positive effect on bone health in women, so it’s particularly exciting to find that prunes can also play a beneficial role in men’s bone health. We look forward to continuing to study the ‘prune effect’ on bone and other health outcomes in men,” said lead researcher Professor Shirin Hooshmand at San Diego State University.
In this study, 57 healthy men aged 50-79 years old were randomised to either consume 100 grams of prunes every day or no prunes for twelve months. After a year, the prune consumers showed significant decreases in biomarkers of bone breakdown, while no changes were observed in the control group. The study authors also reported the men who ate prunes showed improvements in bone geometry indicating greater bone strength.
Historically, research has focused on osteoporosis and bone health in women, already indicating a favorable bone response to prunes specifically among postmenopausal women. Several studies have suggested that eating 50 to 100 grams of prunes everyday could lead to increased bone mass and decreased bone breakdown. Moreover, a recent case study earlier this year reported that total bone mineral density increased in a postmenopausal woman with osteopenia after she consumed 50 grams of prunes daily for 16 months.
“Bone health is not just a concern for women. Men need to think about how to protect their bones as well,” said Leslie Bonci, MPH, RDN and consultant with the California Prune Board. “Prunes are a shelf-stable and nutrient-packed food that provide a preventive, proactive, palatable option for men to optimize their bone health.”
While San Diego State University’s newest research is an exciting addition to existing prune-focused literature, more work on the effect of prunes on human bone health is currently underway. An upcoming study from Pennsylvania State University examines how consuming different amounts of prunes affects health outcomes in postmenopausal women over a one-year period. The study not only explores the impact of prunes on bone health, but it will also look at the prune-effect on inflammation and gut health.
