Month: April 2021

Timing is Key for Psychological Treatment of Chronic Pain

When timed correctly, psychological interventions can reduce the risk of chronic pain, according to a pain expert at the virtual 2021 American Academy of Pain Medicine annual meeting.

“We can look at chronic pain as occurring in a very linear process,” said Ravi Prasad, PhD, of University of California Davis, in a meeting session about multimodal ways to prevent chronic post-surgical pain.

“By definition, pain starts off as something acute,” Dr Prasad explained. The acute phase includes assessments and treatment to try to eliminate pain quickly.

“When the pain condition fails to respond to some of these initial treatments, it starts to enter the subacute category,” Dr Prasad continued. “The patient is still engaged in different medical workups to try to identify the cause of the pain and still participating in treatments, but they haven’t responded to the interventions in the manner expected, meaning the pain continues to persist.” Normally, this comes some 3 to 6 months after the acute phase.

Pain can become chronic when it has plateaued and resists medical treatment for at least 6 months.

“It’s important to recognize these time points exist,” Dr Prasad emphasised. “We can intervene at these different points — and intervene even prior to the experience of acute pain — to try to minimize the likelihood that persistent pain develops.”

There are many factors which contribute to chronic pain. These include environmental stressors, lifestyle factors, unhealthy support systems, limited care access, and patient risk factors such as substance abuse history, adverse childhood experiences, and psychiatric conditions.

Research has shown the most useful predictors of poor pain outcomes after surgery were pre-surgical somatization, depression, anxiety, and poor coping.

“All of these are things that are actually modifiable,” Prasad said. “We can actually do something about these to change the outcomes a person might have.”

Cognitive therapies and relaxation training are two interventions receiving a lot of attention, he noted. Breathing, relaxation exercises, and meditative practices can help patients learn to quiet the nervous system by working on the sympathetic-parasympathetic axis. But cognitive processes also have to be targeted, Prasad observed, and “this is where cognitive behavioral therapy can come in.”

Cognitive behavioural theory is premised on the idea that “by changing the interpretation, we can change the impact of consequences at the emotional, physical, and behavioral level,” Dr Prasad said. “The challenge with this is that our interpretations tend to be automatic.”

“Making changes in our interpretation is difficult because we have to become aware of processes that are occurring in our subconscious and make changes in something that’s been with us for a very long period of time,” he acknowledged. “These thought processes can be very resistant to change. But it’s essential we do this if we want to have sustained change in our outcomes.”

It’s not something as simple as turning negative thoughts into positive ones, Prasad added. “Rather, we look at the accuracy and the degree of helpfulness of the thoughts, and modify the thoughts into something that is more accurate and helpful.”

“We know that when people engage in cognitive behavioral therapy, their outcomes are improved. Affective stress is decreased, pain sensitivity decreases, and this can minimize opioid burden,” he continued. He added that there are many psychological-based tools backed by a strong evidence basem including biofeedback training and mindfulness-based stress reduction.

Dr Prasad emphasised however that timing of these treatments is essential.

“The way to optimize timing is to do presurgical screening to identify what’s the most appropriate intervention for the patient,” he said. Some patients may need help before surgery, others can be targeted at the acute or subacute phase. “Regardless, we want to make sure we address symptoms as early as possible and not wait for pain to be in a chronic state.

Source: MedPage Today

Presentation information: Prasad R “Psychological Interventions to Reduce of Persistent Pain” AAPM 2021.

Hiking Prescribed for Elderly Man Coping with Lockdown

When Jim Snodgrass, 84, was expecting to receive medication to treat his anxiety, he instead was simply given the phone number for the Ramblers, a UK-based society of nature walkers and hikers.

Dr Victor Jack said that he recognised that Jim needed “social connection” and not medication. Hiking itself also has a number of proven physical and psychological health benefits. Some may be immediate, such as decreased blood pressure, decreased stress levels, enhanced immune system functioning, and restored attention, or else occur over time, such as weight loss, decreased depression, and overall wellness.

During the first COVID lockdown in March 2020, Jim was on his own since his wife Sheila died six years previously, said he suffered a breakdown.

The grandfather-of-two said: “I was not feeling good as I was bothered with my nerves so I called the doctor and that’s when I burst into tears on the phone to the receptionist.

“She was so nice to me and got the doctor to call me. I was surprised when he didn’t give me any pills and instead gave me the number for the Ramblers.”

During lockdown doctors could give exemptions to people who lived on their own to meet one other person outside. Then last summer people were allowed to meet in groups to walk.

Presently in the UK, groups of 15 people are allowed to meet outside.

He said: “The Ramblers saved me during the last year of lockdowns. I don’t know where I would be without them with my nerves. Within two miles of walking I’m a different person. Dr Jack is an amazing man as he has saved me from my nerves in the lockdowns with this idea of his.”

Jim has walked 6.4 to 8 kilometres a day in the last year.

He said: “I even went out when the roads were icy and always stayed within a five mile radius of South Queensferry during the lockdowns. I hope my story helps someone else who is feeling bad so they know to join their local Ramblers group too.”

Dr Jack, of South Queensferry Medical Practice, told BBC Scotland his own experience with stress was used to inform Jim’s treatment.

“When Jim told me he liked walking but that he had been walking on his own I was aware that he was actually quite socially isolated as his wife had died,” Dr Jack explained. “He was benefitting from the physical part of walking but not the social side. A few years ago I joined a running club and found it very helpful for stress. This has made me recognise that any sports club has a benefit particularly through the social connection it provides.”

Dr Jack said he had seen numerous patients experiencing mental health issues during the lockdown, especially in those working from home.

Brendan Paddy, director of Ramblers Scotland, said: “Jim is truly an inspiration to us all. It’s amazing to see how he’s improved his health and happiness by getting active with his local South Queensferry Ramblers group.

“Clearly lockdown has been a hugely challenging time, yet we know that many more people like Jim are discovering the revitalising power of walking – with booming numbers enjoying Scotland’s outdoors. I’d urge anyone who’d like a bit more adventure, friendship and fresh air in their lives, to give the Ramblers a go.”

Source: BBC News

Earlier, Improved MRI Detects ‘Broken-heart’ Syndrome

A new study from Karolinska Institutet in Sweden suggests that early magnetic resonance imaging (MRI) of the heart can greatly increase the rate of diagnosis of broken-heart syndrome, which can happen when there is no obvious cause in the coronary artery. 

Myocardial infarction is typically caused by a blockage of the coronary artery by a blood clot. However, in up to 10% of all myocardial infarctions, no obvious cause in the coronary artery is found, and so the working diagnosis MINOCA (myocardial infarction with non-obstructive coronary arteries) is given, which can subsequently lead to one of several diagnoses.

Most of these patients are women, many of whom are diagnosed with takotsubo cardiomyopathy (broken-heart syndrome), characterised by reduced heart function that is likely stress-related, presenting the same symptoms as a standard heart attack.

“Around 80 to 90% of broken-heart sufferers are women, and the disease is associated with mental stress,” said principal investigator Per Tornvall, senior physician and professor at the Department of Clinical Science and Education, Stockholm South General Hospital, Karolinska Institutet. “There also seems to be a link to hypersensitivity towards stress caused by low estrogen levels. Unfortunately, research on the investigation and treatment of myocardial infarction is often done on men, while female heart disease is less studied.”

In a prior study with 150 patients, cardiovascular magnetic resonance (CMR) is often done when examining patients with MINOCA. CMR conducted approximately 10 days after onset can result in a diagnosis in under half the patients, normally takotsubo or myocarditis (inflammation of the heart muscle), Now, the same researchers have tested a new, more sensitive CMR technique two to four days after onset on a comparable group of 148 patients. They found that 77% of the patients could be diagnosed: 35% of takotsubo and 17% of myocardial inflammation, compared with 19 and 7%, respectively, in the first study.

“We don’t know how much effect the improved CMR technique has, but the results suggest that with early examination more patients can get a correct diagnosis and therefore the right treatment,” says Professor Tornvall. “The next step is for us to develop the CMR examination with pharmacological stress of the heart. This will enable us to study the smallest of the blood vessels and hopefully find a cause for the 23% who received no diagnosis.”

Source: Medical Xpress

Journal information: Peder Sörensson et al. Early Comprehensive Cardiovascular Magnetic Resonance Imaging in Patients With Myocardial Infarction With Nonobstructive Coronary Arteries, JACC: Cardiovascular Imaging (2021). DOI: 10.1016/j.jcmg.2021.02.021

Treatment of Lingering COVID Pain is Challenging

The treatment of pain in recovered COVID patients poses unique challenges, said a pain expert presenting at the American Academy of Pain Medicine virtual meeting.

“A lot of these patients are going to need rehabilitation” or physical therapy, noted Natalie Strand, MD, of the Mayo Clinic in Scottsdale, Arizona, at the meeting. “There can be quite a bit of deconditioning that occurs, especially after a prolonged ICU stay. Neuropathic pain is also quite common.”

Post-COVID neuropathy may be viral or else possibly related to patient positioning, including prone positioning. Some patients “may need short-term opioids or gabapentinoids and they may experience aggravation of prior underlying pain, either due to direct physical causes or to the increase in anxiety and depression that can accompany a COVID infection,” Dr Strand said.

A study that followed 143 patients two months after acute COVID showed a high proportion reported persistent symptoms — including fatigue (53%), joint pain, (27%) and chest pain (22%) — that often results in patients going to a pain clinic for care, she noted.

Persistent pain remains prevalent, following any ICU admission, ranging from 28% to 77%, according to Dr Strand.

Chronic neuropathic pain after a COVID patient’s ICU stay can include muscle pain related to joint contractures or muscle atrophy, and pain due to critical illness myopathy or polyneuropathy. In addition, peripheral nerve injuries have been associated with prone positioning for COVID–related acute respiratory distress syndrome, Dr Strand added. Complications from traumatic procedures like placement of chest tubes or tracheotomy can also cause chronic neuropathic pain.

Dr Strand noted that pain can persist after discharge of COVID patients, as indicated by follow-ups. In China, three-quarters of patients previously hospitalised with COVID continued to report at least one symptom 6 months later, with fatigue or muscle weakness by far the most common symptoms (63%). “Compared with 2-month follow up, 6 months later we see the same trends,” she pointed out.

In that study, “13% of the patients who did not develop an acute renal injury during their hospital stay and presented with normal renal function exhibited a decline in GFR at follow up,” Dr Strand noted. This may signal caution about using NSAIDS to manage pain in some patients, she said: “Normal renal function at discharge does not necessarily mean it will remain this way 6 months afterwards.”

There may be a relationship with the SARS-CoV-2 virus and chronic neuropathic pain, Strand observed. In a recent article in Pain Reports, “the authors concluded it could be direct or indirect effects of the virus on the nervous system that can cause neuropathic pain,” she noted. “We know that there are neuropathic symptoms involved with the famous loss of taste and loss of smell with presentation,” she continued. “But also in the acute phase, we commonly see headache, dizziness, muscle pain, ataxia, and in hospitalized patients we see stroke, meningitis, encephalitis, and autoimmune disorders like Guillain-Barré syndrome and acute disseminated encephalomyelitis.”

Psychological stressors can also be related to the emergence of chronic pain, added Dr Strand. “Anxiety and depression often follows COVID-19 infection,” she said. “It may be wise to screen our patients for anxiety and depression after infection to see if we can further control these components to help manage their pain overall.”

Source: MedPage Today

Presentation information: Strand NH “Treating the COVID-Recovered Patient: An Evolving Understanding” AAPM 2021.

Girls at Almost Double The Risk of Concussion in American Football

In high school American football, girls are at nearly double the risk of concussion compared to boys, according to a new study. Girls are also less likely to be removed from play and take longer to recover from the injury than their male counterparts.

Researchers at the University of Pennsylvania and Michigan State University along with Prof Willie Stewart, Honorary Professor at the University of Glasgow reviewed three years of injury data for a population of around 40 000 female high school American footballers in the Michigan High School Athletic Association, comparing them to a similar number of their male counterparts.

They found that, as seen in previous studies, the risk of sports related concussion among female footballers was 1.88 times higher than among males. The researchers also identified several sex-associated differences in sports concussion mechanism and management. This provides new insight into this kind of injury in this demographic. 

Male footballers tended to be injured in collisions with another player and were 1.5 times more likely than females to be removed from play on the day of injury. Female footballers were most often injured from impacts involving equipment, such as the ball or a goalpost, and also took on two days longer on average to recover from injury and return to play. A recent study however showed no differences for concussion recovery time among male and female college athletes, but there could be differences depending on the type of sport.

These sex-associated differences among teenage athletes in mechanism of injury and in management and outcomes of concussion raise the question of whether sports should consider the adoption of sex specific approaches to both participation and concussion management.

Lead author Dr Abigail Bretzin, postdoctoral fellow and certified athletic trainer at the University of Pennsylvania, said: “This is the first study to look in this detail at sex-associated differences in concussion management and outcomes in teenage footballers. Our findings add to research showing that female athletes are at increased concussion risk compared to male athletes, and highlight the importance of sex-specific research in this field.”

Senior author Prof Stewart, said: “Given we know the importance of immediate removal from play for any athlete with suspected concussion, it is notable that “if in doubt, sit them out” appears more likely to happen for boys than girls. This, together with the finding that mechanism of injury appears different between boys and girls, suggests that there might be value in sex-specific approaches to concussion education and management in this age group.”

Source: Medical Xpress

Journal information: Abigail C. Bretzin et al. Association of Sex With Adolescent Soccer Concussion Incidence and Characteristics, JAMA Network Open (2021). DOI: 10.1001/jamanetworkopen.2021.8191

Trump Encouraged to Urge Followers to Take Vaccine

As US polls show that half of Republicans voters are reluctant to get a COVID vaccine, two former senior Trump administration officials have said that former US President Donald Trump is being encouraged to urge his followers to get the jab. 

The officials stressed that herd immunity could be threatened by Republican vaccine hesitancy, and that Trump’s followers will listen to him and him alone.

“Vaccines are widely regarded as one of Trump’s greatest accomplishments, and Trump understands that this legacy is at risk because half of his supporters are not taking the vaccine,” one of the officials told CNN. “It’s just not clear yet if he understands that he’s the only one who can fix this.”

The other official concurred. “In Trump country, if you want to call it that, there are still significant numbers of people who aren’t sure [COVID] is a real thing, despite folks getting sick, and there are lots of suspicions about the vaccine,” the source said. “They have literally said to me, ‘I want to hear from the president about this.’ I don’t think they’re going to listen to anyone else.”

Trump told Fox News last week that he would make a “commercial” about the vaccine, but did not make a firm commitment.
However, a person close to Trump disagreed he should take this approach. “He shouldn’t be pushing these vaccines. His posse isn’t exactly vaccine-approving and it could backfire,” the person said.

All the living former presidents save for Trump, and their wives, appeared in an ad campaign started last month encouraging vaccination – though Trump’s team denied he was approached to participate. This was because the team that organised the PSA did not think it was likely he would participate, according to a source close to that project.

In the Fox interview, Trump said, “I encourage them to take it. I do,” referring to his supporters, but has only spoken out a few times about vaccination.

Fifty-four percent of Republicans are either hesitant about or opposed to getting a COVID vaccine, according to a March survey by the Kaiser Family Foundation, and 29% said they would not get a vaccine under any circumstances.

The number of people 18 and over with at least one vaccine dose, the top 10 states are all states President Joe Biden won last November. Trump won 9 out of the bottom 10 states for vaccination.

A third former Trump official confided that as early as last summer, there were already concerns over Republican vaccine refusal.

“On Facebook I saw a ton of hesitancy for that group — just insane amounts of hesitancy already and we knew it was just going to get worse,” the official said.

That official said Trump ally Michael Caputo briefly mentioned to Trump last fall that it would be good for the president to do a vaccine PSA after the election.

One of the other former officials noted that recently, Caputo “in particular has been active in discussing” the possibility of doing a PSA with the Trump team.

“Michael takes this very seriously and sees this as a big public health problem,” said the source. “His stepping out, because he’s so connected to the president, is really going to be forceful and incredibly helpful.”

Mr Caputo served as assistant secretary for public affairs at the US Department of Health and Human Services, leaving after being diagnosed with throat cancer and a rant at heath scientists saying they were undermining Trump.

Mr Caputo confirmed to CNN that he met with Trump and the two men “spoke about vaccine hesitancy and what can be done about it.”

Trump’s final year in office will define his legacy, according to historians, which was marred by the failure to contain COVID and his incitement of a mob that stormed the US Capitol.

The former  officials said they don’t want to see the vaccine development that Trump pushed undone by vaccine hesitancy, including among his own supporters.

“I see Operation Warp Speed tipping towards failure, and it really concerns me,” one of the senior officials warned. “If we don’t move half those people into the vaccinated column, we’re most likely not going to reach community immunity, and if we don’t reach it, then the president’s vaccine legacy is dead.”

The other senior official said Trump supporters would respond positively to the former president “taking ownership of Operation Warp Speed” and mentioning that he and his wife were both vaccinated.

“He could talk about how [vaccine uptake] is the way to get the country back to where it needs to be economically and socially, using his language that he uses with his supporters. I think that would be really powerful,” said the source.

Source: CNN

‘Nanotraps’ Capture COVID Virus and Prevent Infection

Researchers have developed an entirely new treatment for COVID: ‘Nanotraps’ that capture the viruses inside the body, allowing the immune systems to destroy them

The “Nanotraps” mimick the human cells the virus normally attaches to, and bind it to their surface, keeping the virus from reaching other cells and target it for destruction by the immune system. It is possible that Nanotraps could be used on SARS-CoV-2 variants, and could be administered as a nasal spray.

“Since the pandemic began, our research team has been developing this new way to treat COVID-19,” said Assistant Professor Jun Huang, whose lab led the research. “We have done rigorous testing to prove that these Nanotraps work, and we are excited about their potential.”

Postdoc Min Chen and graduate student Jill Rosenberg targeted the spike mechanism that SARS-CoV-2 uses to lock onto ACE2 proteins on human cells.

To create a trap that would bind to the virus in the same way, they designed nanoparticles with a high density of ACE2 proteins on their surface. Other nanoparticles were designed with neutralising antibodies on their surfaces.

ACE2 proteins and neutralising antibodies have both been used in COVID treatments, but by mounting them onto nanoparticles, a much more effective and robust means for trapping the virus was created.

The nanoparticles are smaller than cells, 500 nanometres in diameter, allowing them to reach deep inside tissue and trap the virus.

No evidence of toxicity was seen in tests with mice, and they then tested the Nanotraps against a non-replicating virus called a pseudovirus in human lung cells in tissue culture plates and saw that they completely prevented viral entry into the cells.

 When the nanoparticle binds to the virus (about 10 minutes after injection), it chemically signalled macrophages to engulf and destroy the nanoparticle and the attached virus. Macrophages normally engulf nanoparticles, so this merely sped up the process.

Testing the Nanotraps on a pair of donated lungs kept alive with a ventilator, they found that they completely prevented infection.

They also collaborated with researchers at Argonne National Laboratory to test the Nanotraps with a live virus (rather than a pseudovirus) in an in vitro system. They found a 10 times better performance than with neutralising antibodies or ACE2 inhibitor.

The researchers plan further tests, including live virus and its variants.

“That’s what is so powerful about this Nanotrap,” Rosenberg said. “It’s easily modulated. We can switch out different antibodies or proteins or target different immune cells, based on what we need with new variants.”

Storage is simple, as the Nanotraps can be kept in a standard freezer, and administration is simple, using a nasal spray. The researchers said it is also possible to serve as a vaccine by optimisation of the Nanotrap formulation.

Source: Phys.Org

Journal information: Min Chen et al, Nanotraps for the containment and clearance of SARS-CoV-2, Matter (2021). DOI: 10.1016/j.matt.2021.04.005

Loss of Smell and Taste in COVID Explained

Cut lemon. Photo by Karolina Grabowska from Pexels

New research awaiting peer review uncovers why the loss of sense of taste is one of the symptoms of COVID infection.  New research has found that taste receptors have ACE2 and are also at risk for SARS-CoV-2 invasion.

Understanding the presence of viral infection in taste buds could help treat people with ‘long COVID’ who could continue to experience changes in or loss of taste months after the initial infection.

SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) enzyme attached to the membranes of cells as their point of entry. ACE2 enzymes are present all over the body, especially in the lungs and nose, coinciding with COVID’s early symptoms of loss of smell and difficulty breathing. Loss of taste is another early COVID infection sign, although the mechanism behind this is unclear. 

“By demonstrating the co-localization of SARS-CoV-2 virus, Type II taste cell marker, and the viral receptor ACE2, we show evidence for replication of this virus within taste buds that could account for acute taste changes during active COVID-19,” wrote the authors. “This work also shows that the proliferation of the taste stem cells in recovering patients may take weeks to return to their pre-COVID-19 state, providing a hypothesis for more chronic disruption of taste sensation, reports of which are now appearing in the medical literature.”

Source: Wikimedia. CC0 Creative Commons
Diagram of the tongue. The fungiform papillae is located near the centre of the tongue.

ACE2 is present on Type II taste bud cells on the tongue. There are three cranial nerves (CN VII, IX and X) that are involved in relaying taste information to the central nervous system. Taste is first discriminated in taste receptor cells (TRCs) within taste buds located in circumvallate (CVP), foliate (FLP) and fungiform papillae (FP) in the tongue. Three defined TRCs relay five basic tastes. Stem cells around the taste bud receive signals from taste cells, prompting differentiation into a replacement TRC. 

The researchers identified 5000 to 10 000 taste buds, with almost half located at the base of the tongue called circumvallate papillae. ACE2 was found to be coexpressed with phospholipase C β2 used in the signaling of type II taste receptor cells. Taste receptor cells in the back of the tongue, a region known as fungiform pallipae, also had ACE2 receptors, providing further evidence of a viral entry point for SARS-CoV-2.

“Replication of virus can likely then occur undisturbed and allow for transmission from the taste bud into circulation, and locally infect lingual and salivary gland epithelium, oral mucosa and larynx and even on into the lungs,”

Case Studies of Altered Taste During and After COVID Infection

A 45-year old woman with COVID and controlled hypertension reported changes in her sense of taste, including not being able to taste the sweetness from chocolate and describing curry as ‘white’ and her tongue was enlarged and redder around the fusiform pallipae.

SARS-CoV-2 RNA was found in samples taken from that area, specifically in PLCB2 positive cells. The virus was also found in the lamina propria with disruptions in the stem cell layer. Symptoms improved after six weeks, along with taste perception.

A 63-year-old man with no preexisting conditions had donated samples of his fusiform pallipae in 2019, and more samples were taken six weeks after testing positive for COVID. He experienced several long COVID symptoms, including mild loss of taste — coffee tasted like mud, and he could not taste chocolate. The virus was not present in samples of his fusiform pallipae 10 weeks after infection. However, he had altered changes to the stem cell layer of the tongue compared to the 2019 samples.

The researchers suggested that stem cell impairments may affect taste bud cell turnover and could contribute to the delayed return of sense of taste.

Source: News-Medical.Net

Journal information: Doyle ME, et al. Human Taste Cells Express ACE2: a Portal for SARS-CoV-2 Infection. bioRxiv, 2021. doi: https://doi.org/10.1101/2021.04.21.440680
https://www.biorxiv.org/content/10.1101/2021.04.21.440680v1

New High-yield Vaccine Technology Recycles Cell Junk

As the world struggles with COVID vaccine production bottlenecks and scaling issues, a team from Northwestern University synthetic biologists have developed a high-yield vaccine technology, increasing production of protein-based vaccines by a factor of five.

Scaling up COVID vaccine production has proved extremely challenging. Adenovirus vaccines such as AstraZeneca’s need to be cultured in 2000 litre tanks containing human cells and then extracted, while mRNA vaccines like that produced by Pfizer requires very careful mixing, as well as components and only a few companies have the skills to produce them. The promising protein subunit vaccines such as Novavax’s offering may be easier to scale up, but also require specific adjuvant, which uses saponin from the bark of a Chilean tree, Quillaja saponaria, which is also used in other vaccines.

Earlier this year, the researchers introduced a new biomanufacturing platform that can quickly make shelf-stable vaccines at the point of care, ensuring they will not go to waste due to transportation or storage problems. In this new study, the team found that enriching cell-free extracts with cellular membranes—the components needed to made conjugate vaccines—massively boosted yields of its freeze-dried platform.

The new technology can produce 40 000 doses per litre per day of antibiotics or vaccines, costing about $1 per dose. At that rate, the team could use a 1000 litre reactor to generate 40 million doses per day, reaching 1 billion doses in less than a month.

“Certainly, in the time of COVID-19, we have all realized how important it is to be able to make medicines when and where we need them,” said study leader Michael Jewett, a professor of chemical and biological engineering at Northwestern. “This work will transform how vaccines are made, including for bio-readiness and pandemic response.”

The new manufacturing platform—called in vitro conjugate vaccine expression (iVAX)—is made possible by cell-free synthetic biology, a process where a cell’s outer wall (or membrane) is removed, and its internal machinery repurposed. This repurposed machinery is then placed in a test tube and freeze-dry it. The cell-free system is activated by the addition of water, turning it into a catalyst for making usable medicine when and where it’s needed. With a shelf-life of over six months, the platform eliminates the need for complicated supply chains and extreme refrigeration, making it extremely valuable for remote or low-resource settings.

In a prior study, Jewett’s team used the iVAX platform to produce conjugate vaccines to protect against bacterial infections, repurposing molecular machinery from Escherichia coli to make a single dose of vaccine in an hour, at $5 per dose.

“It was still too expensive, and the yields were not high enough,” Prof Jewett said. “We set a goal to reach $1 per dose and reached that goal here. By increasing yields and lowering costs, we thought we might be able to facilitate greater access to lifesaving medicines.”

Prof Jewett and his team found that the cell’s membrane, which is typically discarded in cell-free synthetic biology, was key to solving this. When broken apart, membranes naturally reassemble into vesicles, spherical structures that still carry important molecular information. Studying these vesicles, the researchers discovered that increasing vesicle concentration could be useful in making components for protein therapeutics such as conjugate vaccines, which work by attaching a sugar unit—that is unique to a pathogen—to a carrier protein. 

Normally attaching the sugar unit to the protein is very complex, but the researchers found that the cell’s membrane contained machinery that enabled the sugar to more easily attach to the proteins. When they enriched vaccine extracts with this membrane-bound machinery, the researchers significantly boosted usable vaccine yields.

“For a variety of organisms, close to 30% of the genome is used to encode membrane proteins,” said study co-author Neha Kamat, who is an assistant professor of biomedical engineering at McCormick and an expert on cell membranes. “Membrane proteins are a really important part of life. By learning how to use membrane proteins effectively, we can really advance cell-free systems.”

Source: Phys.Org

Journal information: Improving cell-free glycoprotein synthesis by characterizing and enriching native membrane vesicles, Nature Communications (2021). DOI: 10.1038/s41467-021-22329-3

People Most in Need of PrEP Don’t Use It

Though sexual minority men and transgender women are aware of pre-exposure prophylaxis (PrEP), a daily pill to prevent HIV infection, few are currently taking it, a New York-based study has found.

The study, published in the journal AIDS and Behavior, surveyed 202 young sexual minority men and transgender women, who are two high-priority populations for HIV prevention, to better understand the factors in their taking PrEP or not.

According to the Centers for Disease Control and Prevention, sexual minority men are the community most impacted by HIV, making up 69% of all new diagnoses in 2018, and transgender populations are disproportionately affected by HIV and prevention challenges. While Black and Hispanic populations are mostly likely to be newly diagnosed with HIV, PrEP users are more likely to be white.

The research team, who is from the Rutgers School of Public Health’s Center for Health, Identity, Behavior and Prevention Studies (CHIBPS), found that while 98 percent of the study’s participants were aware of PrEP, less than 25 percent were currently taking it.

“It was surprising that so few participants were using PrEP, but we were happy to see that there were no racial or ethnic disparities in who was using it,” Caleb LoSchiavo, Study Co-Author and Doctoral Candidate, School of Public Health, Rutgers University. “I think the study results point to the effectiveness of local efforts to increase the use of PrEP for those who need it most.”

While the study PrEP found no differences in use use, it also found racial and ethnic differences in factors associated with taking it. White participants were more likely to use PrEP with increased age, and were less likely to use it if they held concerns about daily medication use. Participants of colour, however, were more likely to use PrEP if they received information about it from a health care provider and if they had more positive beliefs about its use.

“Our study highlights the importance of clinicians in expanding the use of HIV prevention methods like PrEP among those who need it most, both through informing their patients about PrEP and through combating stigmatizing beliefs about PrEP use,” said senior study author Perry N Halkitis, dean of the Rutgers School of Public Health and director of CHIBPS.

The researchers said that the study emphasised the importance of PrEP education in clinical settings.

“Positive public health messaging about PrEP must reframe risk, combat stigma and normalize preventive healthcare,” LoSchiavo said.

Source: News-Medical.Net

Journal information: Jaiswal, J., et al. (2021) Correlates of PrEP Uptake Among Young Sexual Minority Men and Transgender Women in New York City: The Need to Reframe “Risk” Messaging and Normalize Preventative Health. AIDS and Behavior. doi.org/10.1007/s10461-021-03254-4.