The Wannabe Mayor And His Spokesperson, Unmasked

Interoceptive accuracy differs across life stages, weaker in those with autism
by Zhang Nannan, Chinese Academy of Sciences

Credit: Pixabay/CC0 Public Domain
Interoception is the ability to process and integrate signals originating from oneself internally, including heartbeats and breathing patterns. This ability is important for maintaining homeostasis (i.e., physiological equilibrium at all times) in order to achieve an optimal functional of daily lives. On the other hand, recent findings also suggest that autism spectrum disorders are associated with a wide range of sensory integration impairments including interoceptive accuracy.

However, it is still not clear whether individuals with subclinical features of autism (autistic traits sharing similar but less severe impairments in social and communicative skills comparing to clinically diagnosed cases of autism) also exhibit similar impairments in interoceptive accuracy. It is also not clear how interoceptive ability and its association with autistic traits vary in different age groups.

In order to address this issue, Dr. Raymond Chan's team from the Institute of Psychology of the Chinese Academy of Sciences (CAS) has developed an innovative paradigm involving eye-tracking measures to examine the multidimensional interoception and autistic traits in different age groups.

In so doing, they recruited 114 healthy college students aged 19–22 and explored the correlations among autistic traits and interoceptive accuracy using an "Eye-tracking Interoceptive Accuracy Task" (EIAT), which presents two bouncing shapes and requires participants to look at the one bouncing in synchronous with their real-time heartbeat.

This task requires no verbal report or key-pressing, so it has the advantage over other tasks for exploring interoceptive accuracy in preschool children and individuals with psychiatric disorders or speech impairments.

Their findings showed that autistic traits correlated significantly with the ability to describe and express emotion (alexithymia) but not with the different dimensions of interoception such as interoceptive accuracy (performance of interoceptive ability on behavioural tests), interoceptive sensibility (subjective sensitivity to internal sensations on self-report questionnaires) and interoceptive awareness (personal insight into interoceptive aptitude).

They then recruited 52 preschool children aged four to six, 50 adolescents aged 12–16 and 50 adults aged 23–54 to specifically examine relationship of autistic traits and interoceptive accuracy across the three age groups.

Results showed that interoceptive accuracy evolves from childhood to early adulthood, and then declines with age. Adolescents aged from 12 to 16 years exhibited the highest average accuracy. Finally, curvilinear regression of the whole dataset portrayed the developmental trajectory of interoceptive accuracy as having a reverted U-shape trend that peaks in early adulthood.

Taken together, based on the newly developed innovative task that does not require participants to make verbal reports or key-pressing, Dr. Chan's findings suggest that interoceptive accuracy significantly differs between typically-developing preschool children, adolescents and adults. The study also highlights the need for future study into preschool children with suspected autism spectrum disorders.

This study was supported by a grant from the National Science Foundation of China and the CAS Key Laboratory of Mental Health of the Institute of Psychology. It was published in the Journal of Autism and Developmental Disorders titled "Multidimensional interoception and autistic traits across life stages: Evidence from a novel eye-tracking task."

Study shows brain differences in interpreting physical signals in mental health disorders
by University of Cambridge

Credit: Unsplash/CC0 Public Domain
Researchers have shown why people with mental health disorders, including anorexia and panic disorders, experience physical signals differently.

The researchers, from the University of Cambridge, found that the part of the brain which interprets physical signals from the body behaves differently in people with a range of mental health disorders, suggesting that it could be a target for future treatments.

The researchers studied 'interoception' - the ability to sense internal conditions in the body—and whether there were any common brain differences during this process in people with mental health disorders. They found that a region of the brain called the dorsal mid-insula showed different activity during interoception across a range of disorders, including depression, schizophrenia, eating disorders and anxiety disorders.

Many people with mental health disorders experience physical symptoms differently, whether that's feeling uncomfortably full in anorexia, or feeling like you don't have enough air in panic disorder.

The results, reported in The American Journal of Psychiatry, show that activity in the dorsal mid-insula could drive these different interpretations of bodily sensations in mental health. Increased awareness of the differences in how people experience physical symptoms could also be useful to those treating mental health disorders.

We all use exteroception—sight, smell, hearing, taste and touch—to navigate daily life. But interoception—the ability to interpret signals from our body—is equally important for survival, even though it often happens subconsciously.

"Interoception is something we are all doing constantly, although we might not be aware of it," said lead author Dr. Camilla Nord from the MRC Cognition and Brain Sciences Unit. "For example, most of us are able to interpret the signals of low blood sugar, such as tiredness or irritability, and know to eat something. However, there are differences in how our brains interpret these signals."

Differences in interoceptive processes have previously been identified in people with eating disorders, anxiety and depression, panic disorder, addiction and other mental health disorders. Theoretical models have suggested that disrupted cortical processing drives these changes in interoceptive processing, conferring vulnerability to a range of mental health symptoms.

Nord and her colleagues combined brain imaging data from previous studies and compared differences in brain activity during interoception between 626 patients with mental health disorders and 610 healthy controls. "We wanted to find out whether there is something similar happening in the brain in people with different mental disorders, irrespective of their diagnosis," she said.

Their analysis showed that for patients with bipolar, anxiety, major depression, anorexia and schizophrenia, part of the cerebral cortex called the dorsal mid-insula showed different brain activation when processing pain, hunger and other interoceptive signals when compared to the control group.

The researchers then ran a follow-up analysis and found that the dorsal mid-insula does not overlap with regions of the brain altered by antidepressant drugs or regions altered by psychological therapy, suggesting that it could be studied as a new target for future therapeutics to treat differences in interoception.

"It's surprising that in spite of the diversity of psychological symptoms, there appears to be a common factor in how physical signals are processed differently by the brain in mental health disorders," said Nord. "It shows how intertwined physical and mental health are, but also the limitations of our diagnostic system—some important factors in mental health might be 'transdiagnostic', that is, found across many diagnoses."

In future, Dr. Nord is planning studies to test whether this disrupted activation could be altered by new treatments for mental health disorders, such as brain stimulation.

Increased risk of dying from COVID for people with severe mental disorders
by Umea University

Credit: Unsplash/CC0 Public Domain
People with severe mental disorders have a significantly increased risk of dying from COVID-19. This has been shown in a new study from Umeå University and Karolinska Institutet in Sweden. Among the elderly, the proportion of deaths due to COVID-19 was almost fourfold for those with severe mental disorders compared to non-mentally ill people in the same age.

"We see a high excess mortality due to COVID-19 among the elderly with severe mental disorders, which gives us reason to consider whether this group should be given priority for vaccines," says Martin Maripuu, associate professor at Umeå University.

In the current study, the researchers studied data covering the entire Swedish population over the age of 20 during the period from 11 March to 15 June 2020. Among citizens with severe mental disorder, 130 people died from COVID-19 during this period, which corresponded to 0.1 percent of the group. Among people who had not been diagnosed with a severe mental disorder, the mortality rate was almost halved, 0.06 percent.

Above all, after the age of 60, people with severe mental disorders had a higher excess mortality compared with the general population of the same age. In the age group 60-79 years, death from COVID-19 was almost four times as common among people with a severe mental disorders.

In the study, severe mental disorder was referred to as psychotic disorders, such as schizophrenia and bipolar disorder. The study did not include depression or anxiety in the term, although these conditions can also be severe.

As to what exactly causes the excess mortality in COVID-19 among people with severe mental disorders, the study itself provides no answer.

"It might be that severe mental disorders can lead to premature biological aging, that the disease impairs health and the immune system in general or that this group has other risk factors such as obesity. It is always important to address both, mental and physical health problems of people with these disorders," says Martin Maripuu.

In total, almost eight million individuals formed basis for the study. The study has been published in the scientific journal Frontiers in Psychiatry.

FEBRUARY 11, 2022

Engineered antibody helps block SARS-CoV-2 transmission
by UC Davis

Engineered FuG1 antibody competitively interferes with the furin function needed for the SARS-CoV-2 virus to become highly transmissible. Credit: UC Davis
Researchers at UC Davis Health have engineered a novel antibody, FuG1, that can directly interfere with the cell-to-cell transmission ability of SARS-CoV-2, the virus that causes COVID-19.

FuG1 targets the enzyme furin, which the virus uses for its efficient chain of infections in human cells. The approach could be added to existing SARS-CoV-2 antibody cocktails for greater function against emerging variants.

A study evaluating the efficacy of the engineered antibody was published today in Microbiology Spectrum.

"We developed an approach that interferes with the transmission chain of SARS-CoV-2. The COVID-19 vaccines are a great lifesaver in reducing hospitalizations and severe illness. Yet, we are now learning that they may not be as effective in controlling the transmissibility of the virus," said Jogender Tushir-Singh, senior author of the study.

Tushir-Singh is an associate professor in the Department of Medical Microbiology and Immunology and a member of the UC Davis Comprehensive Cancer Center therapeutics program. His research uses rational protein engineering to generate multi-targeting antibodies as cancer therapeutics. When the pandemic hit, he began thinking of similar strategies that might work to limit the spread of the coronavirus.

Enzyme activates SARS-CoV-2 spike protein

Furin, found throughout the human body, is involved in various functions of cells. It is a type of enzyme, a protease, that can break down proteins into smaller components. It does this by cutting, or cleaving, the polybasic peptide bonds within the proteins.

In cleaving these bonds, furin often acts as a switch, changing an inactive protein into an active one. For example, furin cleaves the inactive proparathyroid hormone into parathyroid hormone, which regulates calcium levels in the blood.

It can also cleave and activate viruses that enter human cells. Pathogens that utilize furin in their human host include HIV, influenza, dengue fever and SARS-CoV-2.

COVID-19 virus exploits host furin system

When SARS-CoV-2 infects a human cell, it is in its active state, having already "cleaved" its spike protein, a key protein that binds to ACE2 receptors to gain entry.

But when the virus is being synthesized within the host cell—when it is replicating—the spike is in an inactive state. The virus needs to use the host cell's furin to cut the spike protein into two parts, S1 and S2, which makes the spike active on the viral particles for efficient transmissibility upon release.

"The virus exploits the host's furin to transmit from one cell to another and another. This added activation step is what makes the virus highly transmissible," said Tanmoy Mondal, the first author for the study and a post-doctoral researcher at UC Davis Health.

But inhibiting furin to limit the SARS-CoV-2 chain of infection cycle is not a straightforward mechanism.

"Furin is found throughout the human body and is needed for the normal functioning of many biological processes. Stopping furin from doing its job causes high body toxicity. That is why the standard furin inhibitor drugs are not a clinically feasible option," Tushir-Singh said.

Instead, he and his team engineered a conjugated antibody targeting the SARS-CoV-2 spike protein. The design is similar to therapeutic monoclonal (IgG) antibodies but includes an added feature—Fc-extended peptide—that specifically interferes with the host furin. The researchers named this approach FuG1.

FuG1 allows the interruptions of the furin function to limit spike activation, thus specifically limiting the viral transmissibility during its chain of infection in host cells. The high affinity, variable-domain-targeting spike in FuG1 is key for furin-targeting specificity to avoid potential toxicity.

Antibody interferes with spike cleavage and stability

The team evaluated the engineered furin disrupter, FuG1, in human lung tissue cells. Tests were run with the original SARS-CoV-2 variant and pseudoviruses. They found that:

Adding the furin disruptor peptide did not interfere with the function of the antibody or its ability to bind to the SARS-CoV-2 spike.
FuG1 significantly impacted the spike cleavage at furin sites.
FuG1 additionally interfered with the overall stability of the SARS-CoV-2 spike protein, which in general is necessary for infecting cells and transmissibility of the virus.
The next steps for the team will be a series of experiments in mice. They will also test the engineered antibody against current variants like omicron.

Tushir-Singh is cautiously optimistic that variants such as omicron will not yield many differences. "The FuG1 antibody is logical in targeting the newly acquired biological component of SARS-CoV-2 transmissibility—the furin spike cleavage. Since our approach targets the viral assembly process itself, rather than ACE2 neutralization, as long as newly emerging SARS-CoV-2 variants do not interfere with FuG1 antibody binding, it is highly likely this sort of strategy would interfere with viral transmissibility," Tushir-Singh said.

In addition to targeting SARS-CoV-2, Tushir-Singh thinks this approach could be applied to future coronaviruses or any other virus that utilizes proteases like furin to infect cells for their pathology.

NIH scientists identify mechanism that may influence infectivity of SARS-CoV-2 variants
by National Institutes of Health

Creative rendition of SARS-COV-2 virus particles with spike proteins dotting their surfaces. Image not to scale. Credit: National Institute of Allergy and Infectious Diseases, NIH
Scientists at the National Institutes of Health have found that a process in cells may limit infectivity of SARS-CoV-2, and that mutations in the alpha and delta variants overcome this effect, potentially boosting the virus's ability to spread. The findings were published online in the Proceedings of the National Academy of Sciences. The study was led by Kelly Ten Hagen, Ph.D., a senior investigator at NIH's National Institute of Dental and Craniofacial Research (NIDCR).

Since the coronavirus pandemic began in early 2020, several more-infectious variants of SARS-CoV-2, the virus that causes COVID-19, have emerged. The original, or wild-type, virus was followed by the alpha variant, which became widespread in the United States in early 2021, and subsequently the delta variant, which is the most prevalent strain circulating today. The variants have acquired mutations that help them infect people and spread more easily. Many of the mutations affect the spike protein, which the virus uses to get into cells. Scientists have been trying to understand how these changes alter the virus's function.

"Throughout the pandemic, NIDCR researchers have applied their expertise in the oral health sciences to answer key questions about COVID-19," said NIDCR Director Rena D'Souza, D.D.S., Ph.D. "This study offers fresh insights into the greater infectivity of the alpha and delta variants and provides a framework for the development of future therapies."

The outer surface of SARS-CoV-2 is decorated with spike proteins, which the virus uses to attach to and enter cells. Before this can happen, though, the spike protein must be activated by a series of cuts, or cleavages, by host proteins, starting with the furin enzyme. In the alpha and delta variants, mutations to the spike protein appear to enhance furin cleavage, which is thought to make the virus more effective at entering cells.

Studies have shown that in some cases protein cleavage can be decreased by the addition of bulky sugar molecules—a process carried out by enzymes called GALNTs—next to the cleavage site. Ten Hagen's team wondered if this happens to the SARS-CoV-2 spike protein, and, if so, whether it changes the protein's function.

To find out, the scientists studied the effects of GALNT activity on spike protein in fruit fly and mammalian cells. The experiments showed that one enzyme, GALNT1, adds sugars to wild-type spike protein, and this activity reduces furin cleavage. By contrast, mutations to the spike protein, like those in the alpha and delta variants, decrease GALNT1 activity and increase furin cleavage. This suggested that GALNT1 activity may partially suppress furin cleavage in wild-type virus, and that the alpha and delta mutations overcome this effect, allowing furin cleavage to go unchecked.

Further experiments supported this idea. The researchers expressed either wild-type or mutated spike in cells grown in a dish. They observed the cells' tendency to fuse with their neighbors, a behavior that may facilitate spread of the virus during infection. The scientists found that cells expressing mutated spike protein fused with neighbors more often than cells with the wild-type spike. Cells with wild-type spike also fused less often in the presence of GALNT1, suggesting that its activity may limit spike protein function.

"Our findings indicate that the alpha and delta mutations overcome the dampening effect of GALNT1 activity, which may enhance the virus's ability to get into cells," said Ten Hagen.

To see if this process might also occur in people, the team analyzed RNA expression in cells from healthy volunteers. The researchers found wide expression of GALNT1 in lower and upper respiratory tract cells that are susceptible to SARS-CoV-2 infection, indicating that the enzyme could influence infection in humans. The scientists theorized that individual differences in GALNT1 expression could affect virus spread.

"This study suggests that GALNT1 activity may modulate viral infectivity and provides insight into how mutations in the alpha and delta variants may influence this," Ten Hagen said. The knowledge could inform future efforts to develop new interventions.

COVID-19 antibodies remain in the body 10 months after infection
by King's College London

Credit: Pixabay/CC0 Public Domain
A study published in Nature Microbiology looked at the antibodies of 38 patients and healthcare workers in St Thomas' Hospital who were infected within the first wave of COVID-19, before they were vaccinated.

Despite an initial decline in antibody levels just after infection, results showed that most people (18/19 patients) maintained detectable antibody levels 10 months after they were infected.

Antibodies help to fight COVID-19 by binding to the SARS-CoV-2 virus, preventing the virus from infecting cells. These results show how long antibodies remain in the body to fight future infections.

The researchers, led by Dr Katie Doores from the School of Immunology & Microbial Sciences, also tested how antibodies that were created to fight against a specific SARS-CoV-2 variant would respond to other variants. They looked at the original SARS-CoV-2 variant, as well as the alpha, beta, and delta variants.

While antibodies from a specific SARS-CoV-2 variant were able to generate a strong response to an infection from their own variant, results showed that antibodies were less effective when fighting against different variants.

Antibodies bind to the spike protein on the SARS-CoV-2 virus, and vaccines mimic this protein to create the immune response against SARS-CoV-2.

Mutations in the new SARS-CoV-2 variants (alpha, beta, delta) have created concerns about whether the vaccines that were developed to target the original SARS-CoV-2 variant would be effective against the new variants, and whether new vaccines should be designed against these variants.

Dr Liane Dupont said that "this study provides unique insight into the cross-neutralizing antibody responses induced by different SARS-CoV-2 variants."

However, these results suggest that there were differences in the spike protein of alpha, beta, and delta variants. This means that vaccines designed around one of these new variants may be less effective against other variants.

These results also show that our current vaccines designed around the original SARS-CoV-2 variant provides the best protection against all variants and should be used for vaccination programs.

This research follows on from a previous study, also led by Dr Katie Doores, that looked at COVID-19 antibody responses within three months.

Dr Katie Doores added that "this research was possible due to the close collaboration with clinical colleagues at St Thomas' Hospital who were able to sequence the viruses infecting hospitalized patients.

Structural changes in the SARS-CoV-2 Alpha and Beta variants identified
by Children's Hospital Boston

Mutations in the SARS-CoV-2 variants cause changes in the electrostatic potential (electric charge at rest) on the spike surface. Here, positively charged areas are shown in blue and negatively charged areas in red. In the Beta variant, the receptor-binding domain (RBD) and N-terminal domain (NTD) have changed substantially, affecting the ability of antibodies to bind to and neutralize the virus. Credit: Bing Chen, PhD, Boston Children's Hospital
New SARS-CoV-2 variants are spreading rapidly, and there are fears that current COVID-19 vaccines won't protect against them. The latest in a series of structural studies of the SARS-CoV-2 variants' "spike" protein, led by Bing Chen, Ph.D., at Boston Children's Hospital, reveals new properties of the Alpha (formerly U.K.) and Beta (formerly South Africa) variants. Of note, it suggests that current vaccines may be less effective against the Beta variant.

Spike proteins, on the surface of SARS CoV-2, are what enable the virus to attach to and enter our cells, and all current vaccines are directed against them. The new study, published in Science on June 24, used cryo-electron microscopy (cryo-EM) to compare the spike protein from the original virus with that the Alpha and Beta variants.

The structural findings indicate that mutations in the Beta variant (also known as B.1.351) change the shape of the spike surface at certain locations. As a result, neutralizing antibodies induced by current vaccines are less able to bind to the Beta virus, which may allow it to evade the immune system even when people are vaccinated.

"The mutations make antibodies stimulated by the current vaccine less effective," says Chen, from the division of Molecular Medicine at Boston Children's. "The Beta variant is somewhat resistant to the current vaccines, and we think a booster with the new genetic sequence can be beneficial for protecting against this variant."

However, the study also found that mutations in the Beta variant make the spike less effective in binding to ACE2—suggesting that this variant is less transmissible than the Alpha variant.

Reassurance on the Alpha variant; more variant studies underway

As for the Alpha variant (B.1.1.7), the study confirms that a genetic change in the spike (a single amino acid substitution) helps the virus bind better to ACE2 receptors, making it more infectious. However, testing indicates that antibodies elicited by existing vaccines can still neutralize this variant.

To be a heightened threat, the researchers say, a SARS-CoV-2 variant would need to do three things: spread more easily, evade the immune system in vaccinated people or those previously exposed to COVID-19, and cause more severe disease. Fortunately, the Alpha and Beta variants do not meet all these criteria.

"Our data suggest that the most problematic combination of such mutations is not yet present in the existing variants examined here," the researchers write.

Chen's team also plans to report the structures of other variants of concern, including the Delta variant (B.1.617.2), in the near future. Those investigations are still under way.

What should I know about the delta variant?
by Aniruddha Ghosal

What should I know about the delta variant? Credit: AP Illustration/Peter Hamlin
What should I know about the delta variant?

It's a version of the coronavirus that has been found in more than 80 countries since it was first detected in India. It got its name from the World Health Organization, which names notable variants after letters of the Greek alphabet.

Viruses constantly mutate, and most changes aren't concerning. But there is a worry that some variants might evolve enough to be more contagious, cause more severe illness or evade the protection that vaccines provide.

Experts say the delta variant spreads more easily because of mutations that make it better at latching onto cells in our bodies. In the United Kingdom, the variant is now responsible for 90% of all new infections. In the U.S., it represents 20% of infections, and health officials say it could become the country's dominant type as well.

It's not clear yet whether the variant makes people sicker since more data needs to be collected, said Dr. Jacob John, who studies viruses at the Christian Medical College at Vellore in southern India.

Studies have shown that the available vaccines work against variants, including the delta variant.

Researchers in England studied how effective the two-dose AstraZeneca and Pfizer-BioNTech vaccines were against it, compared with the alpha variant that was first detected in the U.K.

The vaccines were protective for those who got both doses but were less so among those who got one dose.

It's why experts say it's important to be fully vaccinated. And it's why they say making vaccines accessible globally is so critical.

COVID-19: How vaccines work against the Delta variant
Credit: Pixabay/CC0 Public Domain
The Delta variant of the coronavirus, first identified in India, is a cause for global concern with studies showing it is more contagious and resistant to vaccines than other forms of COVID.

But there is also evidence vaccines retain important effectiveness against Delta after two doses.

Here is what we know about how variants respond to jabs.

Fewer antibodies...

Several lab tests show that the Delta variant seems to have stronger resistance to vaccines than other variants do.

A British study published in The Lancet medical journal in early June looked at levels of neutralising antibodies produced in vaccinated people exposed to the Delta, Alpha (first identified in Britain) and Beta (first identified in South Africa) variants.

It found that antibody levels in people with two doses of the Pfizer/BioNTech shot were six times lower in the presence of the Delta variant than in the presence of the original COVID-19 strain on which the vaccine was based.

The Alpha and Beta variants also provoked lower responses, with 2.6 times fewer antibodies for Alpha and 4.9 times fewer for Beta.

A French study from the Pasteur Institute concluded that neutralising antibodies produced by vaccination with the Pfizer/BioNTech jab are three to six times less effective against the Delta variant than against the Alpha variant.

... but vaccines still work

Although they represent an essential marker, the levels of antibodies measured in a lab are not enough to determine the efficacy of a vaccine.

In particular they do not take into account a second immune response in the form of killer T cells—which attack already-infected cells and not the virus itself.

As a result, real-world observations are crucial to measuring vaccine effectiveness—and the first results are reassuring.

According to data published on Monday by Public Health England, vaccination with Pfizer/BioNTech and AstraZeneca is as effective at preventing hospitalisation in the case of the Delta variant as it is in the case of the Alpha variant.

Two doses of the Pfizer/BioNTech jab prevent 96 percent of hospitalisations due to the Delta variant, while AstraZeneca prevents 92 percent, according to a study involving 14,000 people.

Previous data released by British health authorities at the end of May come to similar conclusions for less serious forms of the illness.

The Pfizer/BioNTech vaccine is 88 percent effective against symptomatic COVID caused by the Delta variant two weeks after the second dose, while the jab is 93 percent effective for cases caused by the Alpha variant.

AstraZeneca shows efficacy of 60 percent against cases caused by the Delta variant and 66 percent in the case of Alpha.

Scottish authorities published similar data on Monday in The Lancet.

The team behind the Sputnik V jab meanwhile tweeted on Tuesday that theirs was "more efficient against the Delta variant... than any other vaccine that published results on this strain so far".

They did not publish results but said the study by the Gamaleya Center, a Russian research institute, had been submitted for publication in an international peer-reviewed journal.

One dose not enough

Among authorised vaccines only one—developed by Janssen—is given in one dose instead of two, and not enough data exists to determine its effectiveness against the Delta variant.

For the others, lab and real-world tests both conclude that one dose of any vaccine only gives limited protection against the Delta variant.

"After a single dose of Pfizer-BioNTech, 79% of people had a quantifiable neutralising antibody response against the original strain, but this fell to... 32% for B.1.617.2 (Delta)," says the lab study from June.

The Pasteur Institute found that a single dose of AstraZeneca would have "little to no efficacy" against the Delta variant.

Data from the British government confirms the tendency in real-world scenarios: both vaccines were 33 percent effective against symptomatic cases caused by Delta 3 weeks after the first dose compared to around 50 percent effectiveness against the Alpha variant.

In the UK—where the Delta variant is now responsible for 96 percent of new cases—these findings pushed the government on Monday to reduce the waiting period between doses from 12 weeks to eight for people over 40.

In France the wait has been reduced to three weeks from five for a second dose of the Pfizer/BioNTech and Moderna vaccines.

The Pfizer/BioNTech jab does however offer very high (94 percent) protection against hospitalisation due to the Delta variant after one dose.

Shots and social distancing

Scientists agree that the best defence against the Delta variant is to get a full two-dose vaccination against coronavirus.

Top French scientist Jean-François Delfraissy says creating a "block of vaccinated people" will help keep the Delta variant from spreading throughout the population.

A US study from June 10 points to the importance of vaccination to keeping the list of variants from growing.

"Increasing the proportion of the population immunised with current safe and effective authorised vaccines remains a key strategy to minimise the emergence of new variants and end the COVID-19 pandemic", it says.

Antoine Flahault, who heads up the University of Geneva's Institute of Global Health, insists it is still crucial to observe social distancing, share infection information, and observe restrictions when necessary to "keep virus circulation low".

The more the virus circulates, he says, the more opportunity it has to mutate and generate new variations.

Share

Email

Home
Diseases, Conditions, Syndromes
Home
Vaccination
JUNE 14, 2021

Two jabs mostly prevent hospitalisation with Delta variant: UK body
Credit: Pixabay/CC0 Public Domain
Two doses of COVID-19 vaccines are "highly effective" in preventing hospital admission with the Delta variant, Public Health England said on Monday.

Scientists said two jabs of the Pfizer/BioNTech vaccine stopped the need for in-patient treatment in 96 percent of cases.

With a double dose of the Oxford/AstraZeneca shot, the rate was 92 percent, PHE added.

The findings were published as Britain grapples with a surge in coronavirus cases, most of which were of the Delta strain, which first emerged in India.

The increase is again raising concerns about the potential strain on hospitals, prompting calls to postpone a planned lifting of all social distancing curbs on June 21.

The restrictions have been in place since January, when the Alpha strain of the coronavirus, which was first identified in Kent, southeast England, spread rapidly.

The government, which began a mass-vaccination programme with the Pfizer/BioNTech jab in December last year, is pushing for more people to get two jabs.

PHE said the vaccine effectiveness for the Delta variant is comparable to that for the Alpha strain.

Head of immunisation Mary Ramsay said: "These hugely important findings confirm that the vaccines offer significant protection against hospitalisation from the Delta variant."

Further investigations were under way to determine the level of protection against death from the Delta variant, PHE said, but added that it was expected to be "high".

The public health body looked at 14,019 cases of the new variant in England between April 12 and June 4.

Previous analysis indicated that one dose of vaccine is 17 percent less effective in preventing a person developing symptoms from the Delta variant than the Alpha one.

But the latest research showed there was only a small difference after two doses.

Simon Kolstoe, senior lecturer in evidence-based healthcare at the University of Portsmouth, said the inoculation programme was clearly working.

Nearly 57 percent of the UK's adult population has had two doses, according to government statistics.

But he added: "We can only be confident in lifting all restrictions once we know that the link between large-scale infections and hospital admissions has been broken.

"The vaccine certainly seems to be doing its job in breaking this link but a few more weeks to get more people vaccinated certainly seems like a sensible option."

Delta variant '40 percent more transmissible': UK health minister
Colorized scanning electron micrograph of an apoptotic cell (green) heavily infected with SARS-COV-2 virus particles (yellow), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIH/NIAID
The Delta variant of the coronavirus is estimated to be 40 percent more transmissible than the Alpha variant that caused the last wave of infections in the UK, Britain's health minister said Sunday.
But people who have received two doses of vaccine, should be equally protected against either variant, he added.

"That figure, around 40 percent more transmissible, is indeed the latest advice I have," Health Secretary Matt Hancock told Sky News.

The Delta variant, also known as the Indian variant, is now the dominant strain in the UK, according to Public Health England figures.

It was the Alpha variant, previously known as the Kent variant, that forced the UK into lockdown in January.

Hancock said the 40 percent figure came from the government body of scientific advisors, SAGE.

Concerns are mounting over whether the emergence of the Delta variant threatens the government's provisional June 21 deadline for lifting virus restrictions.

Hancock acknowledged that the Delta variant "does make the calculation more difficult for June 21".

"We'll look at the data for another week and then make a judgement," he told the BBC on Sunday, stressing that the government was "absolutely open" to delaying the lifting of restrictions.

Double vaccinations effective

The minister nevertheless stressed that those who have had two doses of vaccine should be protected against illness from the Delta variant.

Public Health England said last month that research showed double vaccination was similarly effective against both the Kent and Delta variants.

"The best scientific advice I have at this stage is that, after one jab, it's not quite as effective against the new Delta variant, but after both jabs, it is," Hancock told the BBC.

So far hospitalisations are "broadly flat", with very few hospitalised after receiving both vaccine doses, he added.

The UK has so far given more than 27 million people two doses—more than 50 percent of adults—while more than 40 million have had one dose.

Hancock said the government was "taking clinical advice" on whether to extend the vaccination programme to children over 12, who are believed to be playing a major role in spreading the virus. But this would not be mandatory, he added.

UK officials: Vaccines effective against Indian variant
by Sylvia Hui

Credit: Pixabay/CC0 Public Domain
British health officials expressed optimism Sunday that the coronavirus restrictions remaining in England can be lifted in June after an official study found that the Pfizer and AstraZeneca vaccines offer effective protection against the variant first identified in India.

Authorities in Britain have expressed concern in recent weeks that increasing cases of the Indian variant could jeopardize the U.K.'s so-far successful plan to reopen its economy. More than 2,880 cases of the Indian variant have been recorded in England, figures show.

The government has said the variant appears to be more transmissible, but there was still uncertainty about how concerning this was.

Jenny Harries, chief executive of the U.K. Health Security Agency, said officials in England are on track to proceed with the final stage of unlocking the country from June 21 if the public remains cautious.

"It's looking good if people are continuing to observe all of the safety signals," she told the BBC. However, she warned that the Indian variant is starting to become the dominant strain in parts of northwestern England, and people in hotspot areas need to be vigilant.

Health Secretary Matt Hancock also said he was "increasingly confident" the country can follow its unlocking plans.

Their comments came after a study by Public Health England found that two doses of the Pfizer or AstraZeneca vaccines offer "high levels of protection" against symptomatic disease from the Indian variant.

The study, which took place between April 5 and May 16, found that the Pfizer vaccine is 88% effective against the variant after two doses. That compared with 93% effectiveness against the variant first identified in Kent, England, researchers said.

The AstraZeneca jab was 60% effective after both doses against the Indian variant, compared with 66% against the Kent variant.

Both vaccines were only 33% effective against symptomatic disease from the Indian variant three weeks after the first dose.

Tough lockdown rules eased in most parts of the U.K. earlier this month, largely thanks to an efficient vaccine rollout program. Socializing indoors in limited numbers are again allowed in homes, restaurants and pubs, and a blanket ban on traveling abroad was also partly lifted.

Officials have said they plan to reopen nightclubs and allow large events like festivals from June 21 if infection rates continue to stay low.

More than 37.7 million people, or 72% of the adult population, have had their first vaccine dose in the U.K. About 42% have had their second dose.

Newly developed inhaled vaccine delivers broad protection against SARS-CoV-2, variants
by McMaster University

Michael D’Agostino demonstrates how a nebulizer would deliver an inhaled vaccine. A new study has found the McMaster-developed vaccine to be effective against variants of concern. Credit: McMaster University
Scientists at McMaster University who have developed an inhaled form of COVID vaccine have confirmed it can provide broad, long-lasting protection against the original strain of SARS-CoV-2 and variants of concern.

The research, recently published in the journal Cell, reveals the immune mechanisms and significant benefits of vaccines being delivered directly into the respiratory tract, rather than by traditional injection.

Because inhaled vaccines target the lungs and upper airways where respiratory viruses first enter the body, they are far more effective at inducing a protective immune response, the researchers report.

The reported preclinical study, which was conducted on animal models, has provided the critical proof of concept to enable a Phase 1 clinical trial that is currently under way to evaluate inhaled aerosol vaccines in healthy adults who had already received two doses of a COVID mRNA vaccine.

The tested COVID vaccine strategy was built upon a robust tuberculosis vaccine research program established by Zhou Xing, a co-lead author of the new study and a professor at the McMaster Immunology Research Centre and Department of Medicine.

"What we've discovered from many years' research is that the vaccine delivered into the lung induces all-around protective respiratory mucosal immunity, a property that the injected vaccine is lacking," Xing says.

Currently authorized COVID vaccines are all injected.

"We wanted, first and foremost, to design a vaccine that would work well against any variant," explains the study's co-lead author Matthew Miller, an associate professor at McMaster's Michael G. DeGroote Institute for Infectious Disease Research.

The McMaster COVID vaccine represents one of only a handful developed in Canada. The urgent work is a critical mission of Canada's Global Nexus for Pandemics and Biological Threats, which is based at McMaster.

Researchers compared two types of adenovirus platforms for the vaccine. The viruses serve as vectors that can deliver vaccine directly to the lungs without causing illness themselves.

"We can remain ahead of the virus with our vaccine strategy," says Miller. "Current vaccines are limited because they will need to be updated and will always be chasing the virus."

Both types of the new McMaster vaccine are effective against highly transmissible variants because they are designed to target three parts of the virus, including two that are highly conserved among coronaviruses and do not mutate as quickly as spike. All COVID vaccines currently approved in Canada target only the spike protein, which has shown a remarkable ability to mutate.

"This vaccine might also provide pre-emptive protection against a future pandemic, and that's really important because as we've seen during this pandemic—and as we saw in 2009 with the swine flu—even when we are able to rapidly make a vaccine for a pandemic virus, it's already way too late. Millions of people died, even though we were able to make a vaccine in record time," says Miller.

"We have revealed in our report that besides neutralizing antibodies and T cell immunity, the vaccine delivered into the lungs stimulates a unique form of immunity known as trained innate immunity, which is able to provide very broad protection against many lung pathogens besides SARS-CoV-2," Xing adds.

In additional to being needle and pain-free, an inhaled vaccine is so efficient at targeting the lungs and upper airways that it can achieve maximum protection with a small fraction of the dose of current vaccines—possibly as little as 1 percent—meaning a single batch of vaccine could go 100 times further, the researchers say.

"This pandemic has shown us that vaccine supply can be a huge challenge. Demonstrating that this alternative delivery method can significantly extend vaccine supply could be a game changer, particularly in a pandemic setting," says Brian Lichty, an associate professor in the Department of Medicine who co-led the preclinical study along with Miller, Xing and the senior trainees Sam Afkhami and Michael D'Agostino, who are the joint first authors of the study.

Repeated seasonal influenza vaccines also provide kids better protection against future flu pandemics, study finds
by McMaster University

Lead researcher Matthew Miller says children and adults are fundamentally different in their immune responses to influenza virus. Credit: JD Howell/McMaster University
Researchers at McMaster University have found that children who receive years of season-specific flu vaccines develop antibodies that also provide broader protection against new strains, including those capable of causing pandemics.

The same ability does not exist in adults.

The findings, reported today in the journal Cell Reports Medicine, could inform the design of a universal influenza virus vaccine for children, who are especially vulnerable to serious complications from flu, such as pneumonia, dehydration and, in rare cases, death.

"Little is known about how seasonal flu vaccination impacts the immune responses in children, who are a major source of flu transmission and a very high-risk group," explains Matthew Miller, lead author of the study and Associate Professor at the Michael G. DeGroote Institute for Infectious Diseases Research. "Understanding how seasonal vaccination and different vaccine formulations shape childhood immunity is critical for effective prevention."

Children and adults are fundamentally different in their immune responses to influenza virus, explains Miller, whose lab is part of McMaster's Global Nexus for Pandemics and Biological Threats. Unlike small children, most adults have been infected with and vaccinated against flu many times throughout their lives.

"When we give adults vaccines, they make a very specific immune response against seasonal strains," says Miller. "Adults simply don't generate immune responses to seasonal flu vaccines capable of protecting them from pandemic viruses like children can."

The researchers spent three years studying immune responses in children between the ages of 6 months and 17 years. They found that as the children grew older, they became less capable of producing broadly protective antibodies, because of their repeated exposure to influenza, through infection or vaccination.

While COVID-19 related measures such as distancing and masking have also resulted in lower rates of influenza, Miller warns the flu will return, possibly in dangerous forms.

Influenza has caused five pandemics in the last 100 years. The Spanish Flu of 1918-19 killed roughly 50 million people worldwide at a time when the global population was about 1.8 billion—less than a quarter what it is today.

For the study, researchers also compared two forms of vaccine: the conventional flu shot and a nasal spray vaccine that works in the upper respiratory tract, where infection first takes hold.

Both worked equally well at generating broadly protective antibodies, which is welcome news for parents seeking a painless alternative to needles.

"This is an important finding because it means we have flexibility in terms of the type of vaccines we can use to make a universal vaccine for children. We now know that children's immune systems are much more flexible than adults' when it comes to being able to teach them how to make these broadly protective responses," says Miller.

Intranasal flu vaccine with nanoparticles offers robust protection, researchers find
by Georgia State University

Credit: Pixabay/CC0 Public Domain
An influenza vaccine administered through the nose and constructed with nanoparticles that enhance immune response offers strong protection against different influenza virus strains, according to researchers in the Institute for Biomedical Sciences at Georgia State University.

The intranasal vaccine contributed to multifaceted immune responses, leading to robust cross protection against influenza in mice. The vaccine consists of PEI-HA/CpG nanoparticles. PEI (polyethyleneimine), a robust and versatile delivery system, can simultaneously carry antigens (hemagglutinin, HA) that induce an immune response in the body, and adjuvants (CpG) that enhance the body's immune response to an antigen for optimal immunoenhancement.

These comprehensive immune responses and cross protection were long lasting, exhibiting defense from influenza virus over six months after immunization. The findings are published in the journal ACS Applied Materials & Interfaces.

Intranasal vaccination is an ideal approach for infectious respiratory diseases such as influenza. Seasonal influenza vaccines generally induce narrow immune responses that rapidly decline, which leaves populations vulnerable to novel influenza strains. Advancements in influenza vaccine technology are needed to protect against a wide range of influenza viruses. Intranasal vaccination can improve local mucosal immune responses by preventing influenza infection at the portal of virus entry.

In the influenza virus, HA is a protein that plays a crucial role in the early stages of virus infection. Influenza HA has a head region and stalk region. Current influenza vaccines elicit immune responses against the HA head, but this head region is highly changeable and accounts for lowered efficiency against different strains. The HA stalk region is more conservative across different strains of influenza viruses.

Protein antigens that are administered intranasally are usually less able to provoke an immune response, so adjuvants are needed to have highly efficient intranasal vaccines. Adjuvants, such as CpG, can enhance and manipulate immune responses, thus improving the potency and breadth of protection.

"The PEI-HA/CpG nanoparticles show good potential as a cross-protective influenza vaccine candidate," said Dr. Baozhong Wang, corresponding author of the study and a professor in the Institute for Biomedical Sciences at Georgia State. "The combination of PEI and CpG in the PEI-HA/CpG nanoparticle group contributed to the multifaceted immune responses, leading to vigorous cross protection. The incorporation of CpG and antigens into the same nanoparticle enhanced cellular immune responses.

"Our results revealed that the nanoparticles significantly enhanced HA immunogenicity, or the ability to provoke an immune response, providing cross protection against different influenza virus strains. The conserved HA stalk region induced substantial antibodies in the nanoparticle immunization groups."

"Nanoparticle platforms have shown intriguing characteristics and great potentials in the development of next-generation cross-protective influenza vaccines," said Dr. Chunhong Dong, the first author of the study and a postdoctoral fellow in the Institute for Biomedical Sciences. "However, challenges exist to the successful research and development of nanoparticle vaccines. Though no apparent adverse effects were observed in the study, a more comprehensive safety evaluation of the nanoparticle adjuvant system is needed before clinical trials."

Intranasal influenza vaccine enhances immune response and offers broad protection, researchers find
by Georgia State University

Credit: CC0 Public Domain
An influenza vaccine that is made of nanoparticles and administered through the nose enhances the body's immune response to influenza virus infection and offers broad protection against different viral strains, according to researchers in the Institute for Biomedical Sciences at Georgia State University.

Recurring seasonal flu epidemics and potential pandemics are among the most severe threats to public health. Current seasonal influenza vaccines induce strain-specific immunity and are less effective against mismatched strains. Broadly protective influenza vaccines are urgently needed.

Intranasal vaccines are a promising strategy for combatting infectious respiratory diseases, such as influenza. They are more effective than vaccines injected into a muscle because they can induce mucosal immune responses in respiratory tracts, preventing infection at the portal of virus entry. They can also stimulate systemic immune responses throughout the body.

Scientists can overcome vaccine safety concerns and the long production phase of virus-based influenza vaccines by constructing intranasal vaccines with recombinant proteins or peptides. However, these vaccines are poor at producing immune responses, so it's necessary to have potent mucosal adjuvants, substances that enhance the body's immune response to antigens (the molecular structures on pathogens). The absence of appropriate mucosal adjuvants currently hinders the development of such a vaccine.

In this study, the researchers developed an intranasal influenza vaccine using recombinant hemagglutinin (HA), a protein found on the surface of influenza viruses, as the antigen component of the vaccine. HA is integral to the ability of influenza virus to cause infection.

They also created a two-dimensional nanomaterial (polyethyleneimine-functionalized graphene oxide nanoparticles) and found that it displayed potent adjuvant (immunoenhancing) effects on influenza vaccines delivered intranasally. The findings are published in the journal Proceedings of the National Academy of Sciences.

"Conventional flu vaccines predominantly induce antibody responses," said Dr. Baozhong Wang, senior author of the study, principal investigator of the National Institutes of Health grant supporting the study and a professor in the Institute for Biomedical Sciences. "However, recent research demonstrates that lung resident memory T cell responses are indispensable for optimal cross-protection against pulmonary influenza infection. The development of lung resident T cell responses requires vaccination by a respiratory route or influenza virus infection. Our research opens a new path for the development of needle-free and logistically simplified intranasal flu vaccines for cross-protection."

"In our study, we reported for the first time that two-dimensional graphene oxide nanomaterials had a potent adjuvant effect in boosting the immune responses of intranasal hemagglutinin (HA) vaccines," said Dr. Chunhong Dong, lead author of the study and a postdoctoral research Fellow in Dr. Baozhong Wang's lab in the Institute for Biomedical Sciences.

"This study gives new insights into developing high performance intranasal vaccine systems with two-dimensional sheet-like nanoparticles," Dong said. "The graphene oxide nanoparticles have extraordinary attributes for drug delivery or vaccine development, such as the ultra-large surface area for high-density antigen loading, and the vaccine showed superior immunoenhancing properties in vitro and in vivo. The nanoplatform could be easily adapted for constructing mucosal vaccines for different respiratory pathogens."

The study, conducted in mice and cell culture, found the nanoparticles significantly enhanced immune responses at mucosal surfaces and throughout the body in mice. The robust immune responses conferred immune protection against influenza virus challenges by homologous (same) virus strains and heterologous (different) virus strains.

The results are also promising because needle-free, intranasal influenza vaccines possess superior logistical advantages over traditional injectable vaccines, such as easy administration with high acceptance for recipients and the avoidance of biohazardous waste.

Intranasal influenza vaccine spurs strong immune response in Phase 1 study
by NIH/National Institute of Allergy and Infectious Diseases

3-D print of influenza virus. The virus surface (yellow) is covered with proteins called hemagglutinin (blue) and neuraminidase (red) that enable the virus to enter and infect human cells. Credit: NIH
An experimental single-dose, intranasal influenza vaccine was safe and produced a durable immune response when tested in a Phase 1 study published in the Journal of Clinical Investigation. The investigational vaccine, called Ad4-H5-VTN, is a recombinant, replicating adenovirus vaccine designed to spur antibodies to hemagglutinin, a protein found on the surface of influenza viruses that attaches to human cells.

The investigational vaccine was developed by Emergent Biosolutions Inc., (Gaithersburg, Maryland). It was administered intranasally (28 study participants), as an oral capsule (10 participants) and via a tonsillar swab (25 participants) to healthy men and non-pregnant women ages 18 to 49 years.

The participants who received the vaccine intranasally or via tonsillar swab showed significantly higher H5-specific neutralizing antibody levels compared to the group receiving the vaccine capsule orally. The participants who received the intranasal vaccine shed viral DNA for two-to-four weeks, but virus could be cultured for a median of only one day. Participants had evidence of H5-specific CD4+ and CD8+ T-cell responses. Additionally, volunteers who received the intranasal vaccine had high levels of serum neutralizing antibodies at 26 weeks after vaccination, and this level was unchanged at three to five years after a single intranasal dose of the vaccine. The duration of viral shedding correlated with a high magnitude of neutralizing antibody response at week 26. In addition, the intranasal vaccine induced a mucosal antibody response in the nose, mouth, and rectum.

The study authors speculate that replication-competent vector vaccines may have advantages over other types of vaccines because they can express viral proteins at higher levels and for longer durations. Additionally, this type of vaccine induces a mucosal immune response that is critical for limiting transmission of viruses that infect mucosal tissues.

The vaccine platform could be highly adaptable for use against other viruses including HIV and SARS-CoV-2, according to the authors.

Eating prunes may help protect against bone loss in older women
by Katie Bohn, Pennsylvania State University

Credit: Pixabay/CC0 Public Domain
It's already well known that prunes are good for your gut, but new Penn State research suggests they may be good for bone health, too.

In a research review, the researchers found that prunes can help prevent or delay bone loss in postmenopausal women, possibly due to their ability to reduce inflammation and oxidative stress, both of which contribute to bone loss.

"In postmenopausal women, lower levels of estrogen can trigger a rise of oxidative stress and inflammation, increasing the risk of weakening bones that may lead to fractures," said Connie Rogers, associate professor of nutritional sciences and physiology. "Incorporating prunes into the diet may help protect bones by slowing or reversing this process."

The review was recently published in the journal Advances in Nutrition.

Osteoporosis is a condition in which bones become weak or brittle that can happen to anyone at any age, but according to the researchers is most common among women over the age of 50. The condition affects more than 200 million women worldwide, causing almost nine million fractures each year.

While medications exist to treat osteoporosis, the researchers said there is a growing interest for ways to treat the condition with nutrition.

"Fruits and vegetables that are rich in bioactive compounds such as phenolic acid, flavonoids and carotenoids can potentially help protect against osteoporosis," said Mary Jane De Souza, professor of kinesiology and physiology, "with prunes in particular gaining attention in previous research."

According to the researchers, bones are maintained throughout adult life by processes that continually build new bone cells while removing old ones. But after the age of 40, this breaking down of old cells begins to outpace the formation of new ones. This can be caused by multiple factors including inflammation and oxidative stress, which is when free radicals and antioxidants are unbalanced in the body.

Prunes, however, have many nutritional benefits such as minerals, vitamin K, phenolic compounds and dietary fiber—all which may be able to help counter some of these effects.

For their review, the researchers analyzed data from 16 preclinical studies in rodent models, ten preclinical studies and two clinical trials. Across the studies, the researchers found evidence that eating prunes helped reduce inflammation and oxidative stress and promoted bone health.

For example, the clinical trials found that eating 100 grams of prunes—about 10 prunes—each day for one year improved bone mineral density of bones in the forearm and lower spine and decreased signs of bone turnover.

Additionally, eating 50 or 100 grams of prunes a day for six months prevented loss of total bone mineral density and decreased TRAP-5b—a marker of bone resorption—compared to women who didn't eat prunes.

"Taken together, evidence from in vitro, preclinical studies, and limited clinical studies suggest prunes may help to reduce bone loss," Rogers said. "This may be due to altered bone turnover and by inhibiting inflammation and suppressing markers of oxidative stress."

The researchers said one potential mechanism for the effects is prunes triggering a change in the gut microbiome that then lowers inflammation in the colon. This may then lower levels of pro-inflammatory cytokines and markers of oxidative damage.

In the future, the researchers plan to further report on the effects of prune consumption for 12 months on bone outcomes, inflammatory pathways and the gut microbiota in a randomized controlled trial that was led by De Souza.

Men with high levels of body fat may be at risk for osteoporosis
by The Endocrine Society

Men with high levels of body fat have lower bone density and may be more likely to break a bone than those with normal levels of body fat, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

Most studies have shown positive or neutral effects of body fat mass—the weight of fat in your body—on bone health. Lean mass is the entire weight of your body, including organs, skin and bones, minus fat. Health care providers often assume people with higher body weight have high bone density and are at low risk of fracture, and these patients are less likely to be screened for osteoporosis.

"We found that higher fat mass was related to lower bone density, and these trends were stronger in men than women," said Rajesh K. Jain, M.D., of University of Chicago Medicine. "Our research suggests that the effect of body weight depends on a person's makeup of lean and fat mass, and that high body weight alone is not a guarantee against osteoporosis."

The researchers analyzed the bone mineral density and body composition data of 10,814 people under 60 years old from the National Health and Nutrition Examination Survey (NHANES) 2011-2018. They found a strong positive association between lean mass and bone mineral density in both men and women. Conversely, fat mass had a moderately negative association with bone mineral density, especially in men.

"Health care providers should consider osteoporosis screening for patients with high body weight, especially if they have other risk factors like older age, previous fracture, family history, or steroid use," Jain said.

Diabetes, metabolic syndrome in mice treated with novel class of compounds
by Julia Evangelou Strait, Washington University School of Medicine

Researchers at Washington University School of Medicine in St. Louis have shown, in mice, that a new class of compounds they developed can improve several aspects of metabolic syndrome. Such conditions often lead to cardiovascular disease, the leading cause of death worldwide. Pictured are two of the compounds (yellow) in the new class—SN-401 (left) and SN-406 (right). Credit: Susheel K. Gunasekar (Sah Lab), Pratik R. Chheda (Kerns Lab)
A study in mice—led by researchers at Washington University School of Medicine in St. Louis—shows that a new class of compounds the scientists developed can improve multiple aspects of metabolic syndrome. An increasingly common group of conditions that often occur together, metabolic syndrome includes type 2 diabetes, high cholesterol, fat buildup in the liver, and excess body fat, especially around the waist. This syndrome often leads to cardiovascular disease, the leading cause of death worldwide.

The study is published in the journal Nature Communications.

Testing one of the compounds referred to as SN-401, the researchers found it treats diabetes by improving the ability of the pancreas to secrete insulin and boosting the ability of other tissues to utilize that insulin to more effectively remove sugar from the bloodstream. In an effort to optimize the treatment, the researchers fine-tuned the compound—creating a class of related compounds—based on their studies of a key protein called SWELL1 (also LRRC8a). The gradual decline of this protein may have a central role in the development of diabetes and other aspects of metabolic syndrome.

"Our goal is to develop better therapies for cardiovascular disease, including diabetes and metabolic syndrome, which are major risk factors for worsening heart and vascular problems," said senior author Rajan Sah, MD, Ph.D., an associate professor of medicine. "We have many treatments for diabetes, but even with those therapies, cardiovascular disease remains a leading cause of death among patients with type 2 diabetes. There is a need for new treatments that work differently from the current standard-of-care therapies."

The protein Sah and his colleagues studied is called SWELL1 because of its role in sensing the size or volume of cells. Their new research reveals that the protein also helps to control insulin secretion from the pancreas and improve insulin sensitivity, including in skeletal muscle and adipose tissue, the body's fat stores.

Surprisingly, the researchers showed that SWELL1 does both of these seemingly independent tasks because the protein has a previously unknown double life. It acts as a signaling molecule, turning on cellular tasks that govern how well cells use insulin and also facilitates the pancreas' secretion of insulin into the bloodstream.

"This protein, SWELL1, has a sort of dual personality," Sah said. "The compound binds to SWELL1 in a manner that stabilizes the protein complex so as to enhance expression and signaling across multiple tissues, including adipose, skeletal muscle, liver, the inner lining of blood vessels, and pancreatic islet cells. This restores both insulin sensitivity across tissue types and insulin secretion in the pancreas."

Sah and his colleagues showed that the SN-401 compound improved multiple aspects of metabolic syndrome in two groups of mice that each developed diabetes from different causes, one because of a genetic predisposition and the other due to a high-fat diet. In addition to improving insulin sensitivity and secretion, treatment with the compound also improved blood sugar levels and reduced fat buildup in the liver. Most of these studies were conducted with an injected form of the compound, but the researchers showed evidence that it also could be effective if taken by mouth.

The researchers further showed that the compound does not have a big impact on blood sugar in healthy mice, which is important for its potential as a future possible therapy. Current medications for diabetes can result in blood sugar levels that are too low. The evidence suggests that this compound does not lower blood sugar in situations when it doesn't need to.