Tag: 24/5/21

Low Leptin Levels Can Stifle Response to Vaccines

Image source: NCI on Unsplash

Reduced levels of leptin, a metabolic hormone, is linked to poor vaccine antibody responses in the general population, according to research by the University of Queensland.

The researchers made the discovery while investigating the response of several cohorts to the influenza vaccine or hepatitis B vaccine prior to COVID.

Professor Di Yu at the University of Queensland identified a link between the metabolic and immune systems that could be exploited to develop new strategies for improving vaccine protection in vulnerable populations.

“Using multiple advanced techniques in immunology, genetics and biochemistry, our study found leptin directly promoted the development and function of cells which are vital in triggering an antibody response,” Professor Yu said.

“In collaboration with global teams, we identified the reduction of an essential metabolic hormone called leptin was associated with compromised vaccine responses in both young and older individuals.

“As a result, we can now identify those who are at risk of not generating an antibody response after vaccination.”

Leptin is a metabolic hormone mostly produced by fat tissue.

“Vaccines have been known for a very long time to have a different efficacy for individuals,” he said.

“Although our genetics partially contribute to the difference, other factors are also essential. When we are fit and healthy, we have a much better vaccine efficacy.

“If we are healthy, we have a good metabolism and a normal level of leptin, but if we have malnutrition or some disease conditions, we may have a low level of leptin, which may limit our vaccine response and immune protection.”

Professor Yu said that one subject was future research was that many people with obesity and high levels of leptin conversely often had leptin resistance, which could also potentially lead to a poorer vaccine response.

The researchers are hoping to test responses to the COVID vaccines to find biomarkers that could identify people who may not mount a strong vaccine response.

“During the era of the COVID pandemic, the successful vaccination for SARS-CoV-2 is the major hope to bring society back to normalcy. Differing vaccine responses cause a major bottleneck in large-scale vaccination programs,” said Professor Yu.

Source: News-Medical.Net

.Journal information: Deng. J., et al. (2021) The metabolic hormone leptin promotes the function of TFH cells and supports vaccine responses. Nature Communications. doi.org/10.1038/s41467-021-23220-x.

Autism Gene Impedes Neuron Development

Image source: Pixabay

Researchers at the Institute of Science and Technology (IST) Austria have uncovered the role of a high-risk gene in autism spectrum disorder (ASD) and its important role during a critical phase of brain development.

Within the European Union alone, about three million people are affected by an autism spectrum disorder (ASD). Some are only mildly affected and can live independent lives. while others have severe disabilities. What the different forms have in common is difficulty with social interaction and communication, as well as repetitive-stereotypic behaviors. Mutations in a few hundred genes are associated with ASD. One of them is called Cullin 3, and it is a high-risk gene, and a mutation of it almost certainly leads to a disorder. 

To learn more about how the gene affects the brain, PhD students Jasmin Morandell and Lena Schwarz with Professor Gaia Novarino’s research group, turned to mice whose Cullin 3 gene has been partially switched off, comparing them to their healthy siblings. 

The three-chamber sociability test

In a series of behavioural and motoric tests, the team wanted to see if the modified mice mimicked some of the characteristics of patients with this form of autism and could therefore be used as model organisms. In one of these tests, the so-called three-chamber sociability test, a mouse could freely explore three adjacent chambers of a box connected by small doors. Two other mice were put in the outer boxes: One familiar to the studied mouse, the other mouse it had never met. “Healthy mice usually prefer the new over the already familiar mouse,” explained co-first author Jasmin Morandell. However, the mouse with the altered Cullin 3 gene, showed no recognition. The mice also had motor coordination deficits and other ASD-relevant cognitive impairments. This mouse model helped the researchers get to the heart of the problem. 

Dangerous protein buildup

While studying the mouse brain, the researchers noticed a very slight but consistent change in the position of some neurons. These neurons originate from a certain region in the brain, migrating toward the uppermost layers until they find their designated place in the cortex. The process is very sensitive, and even small changes in the speed at which they travel can alter the structure of the cortex. The scientists marked the migrating neurons to trace their movements. “We could observe migration deficits – the neurons are stranded in the lower cortex layers,” described the study’s other co-first author, Lena Schwarz. 

Malformations of the cortex
The reason for their poor movement lay in Cullin 3’s role in taggings old cells for degradation – a process that has to be tightly regulated to prevent proteins from accumulating. To find out which proteins are misregulated when Cullin 3 is defective, Morandell and Schwarz systematically analysed the protein composition of the mouse brain. “We were looking at proteins that accumulate in the mutant brain and found a protein called Plastin 3. Then Gaia [the professor they worked under] came across a poster describing the work of IST Austria’s Schur group in the hallway, and we got very excited,” said Jasmin Morandell. “They independently had been working on Plastin 3 as a regulator of cell motility and had complementary results to ours. That’s when we started working together,” Professor Gaia Novarino remembers.

The protein Plastin 3, which was previously unknown in the context of neuronal cell migration, turned out to have a key part in this process. “If the Cullin 3 gene is deactivated, the Plastin 3 protein accumulates, causing cells to migrate slower and over shorter distances. This is exactly what we saw happening in the cortex of the Cullin 3 mutant mice,” said Lena Schwarz.

Early developmental stage

All this occurs during a very early stage of brain development around halfway through pregnancy. “Determining these critical windows during brain development could be extremely important to fine-tune the treatment of patients with specific forms of ASD,” explained Prof Novarino, who is committed to improving diagnosis and treatment options for people with ASD. “Following up with the research on Plastin 3 could pave the way for some therapeutics. Inhibiting the accumulation of this protein could eventually alleviate some of the symptoms patients have,” Schwarz said.

 “We now know that defective Cullin 3 leads to increased levels of Plastin 3. This tight correlation shows that Plastin 3 protein levels may be an important factor for the control of cell-intrinsic movements,” said Jasmin Morandell. 

Source: IST Austria

Journal information: Jasmin Morandell, Lena A. Schwarz et al. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. DOI: 10.1038/s41467-021-23123-x

Only 1 in 10 Getting Full Diabetes Care in Developing Countries

 Only 1 in 10 people with diabetes in low- and middle-income countries are getting evidence-based, low-cost comprehensive care proven to reduce diabetes-related problems, according to a study published in Lancet Healthy Longevity

That comprehensive package of care – low-cost medicines to reduce blood sugar, blood pressure and cholesterol levels; and counseling on diet, exercise and weight – can help lower the health risks of under-treated diabetes. Those risks include future heart attacks, strokes, nerve damage, blindness, amputations and other disabling or fatal conditions.

The authors analysed data from recent surveys, examinations and tests of over 680 000 people between 25 and 64 worldwide. More than 37 000 had diabetes; more than half of them had a key biomarker of elevated blood sugar but had not yet received a diagnosis.

The researchers have provided their findings to the World Health Organization, which is developing efforts to scale up delivery of evidence-based diabetes care globally as part of an initiative known as the Global Diabetes Compact. The forms of diabetes-related care used in the study are all included in the 2020 WHO Package of Essential Noncommunicable Disease Interventions.

“Diabetes continues to explode everywhere, in every country, and 80% of people with it live in these low- and middle-income countries,” said lead author David Flood, MD, MSc, a National Clinician Scholar at the U-M Institute for Healthcare Policy and Innovation. “It confers a high risk of complications such as including heart attacks, blindness, and strokes. We can prevent these complications with comprehensive diabetes treatment, and we need to make sure people around the world can access treatment.”

Flood worked with senior author Jennifer Manne-Goehler, MD, ScD, of Brigham and Women’s Hospital and the Medical Practice Evaluation Center at Massachusetts General Hospital, to lead the analysis of detailed global data.

In addition to the main finding that 90% of the people with diabetes studied weren’t getting access to all six components of effective diabetes care, the study also finds major gaps in specific care.

For instance, while about half of all people with diabetes were taking a drug to lower their blood sugar, and 41% were taking a drug to lower their blood pressure, only 6.3% were receiving cholesterol-lowering medications. Less than a third had access to counseling on diet and exercise.

These findings show the need to scale-up proven treatment not only to lower glucose but also to address cardiovascular disease risk factors, such as hypertension and high cholesterol, in people with diabetes.

“Diabetes continues to explode everywhere, in every country, and 80% of people with it live in these low- and middle-income countries. We need to make sure people around the world can access treatment.” David Flood, MD, MSc.

Even when the authors focused on the people who had already received a formal diagnosis of diabetes, they found that 85% were taking a medicine to lower blood sugar, 57% for blood pressure, but only 9% for cholesterol. Nearly 74% had received diet-related counseling, and just under 66% had received exercise and weight counseling.

Taken together, less than one in five people with previously diagnosed diabetes were getting the full package of evidence-based care.

Economy and availability of care

The researchers found that generally, the lower the average income of the country and region,  the less evidence-based diabetes care was available.

The nations in the Oceania region of the Pacific had the highest prevalence of diabetes – both diagnosed and undiagnosed – but the lowest rates of diabetes-related care.

However some low-income countries had higher-than-expected rates of good diabetes care, said Dr Flood. The Latin America and Caribbean region had the second highest diabetes prevalence, but had much higher levels of care than Oceania.

Finding out what the countries with high-performing achievements in diabetes care are doing well could provide valuable insights for improving care elsewhere, the authors said. That even extends to informing care in high-income countries like the United States, which does not consistently deliver evidence-based care to people with diabetes.

The study also highlights differences in diabetes diagnoses in different regions and countries. Access to diagnosis enables people to receive diabetes care.

Women, people with higher levels of education and higher personal wealth, and people who are older or had high body mass index were more likely to be receiving evidence-based diabetes care. Diabetes in people with ‘normal’ BMI is not uncommon in low- and middle-income countries, suggesting more need to focus on these individuals, the authors noted.

The fact that cheap diabetes-related medications are available, and that people can cut risk through lifestyle changes, mean that cost should not be a major barrier, said Flood. In fact, studies have shown that the medications are cost-effective as a preventative measure.

Source: University of Michigan

Journal information: David Flood et al, The state of diabetes treatment coverage in 55 low-income and middle-income countries: a cross-sectional study of nationally representative, individual-level data in 680 102 adults, The Lancet Healthy Longevity (2021). DOI: 10.1016/S2666-7568(21)00089-1

Milk Consumption Does Not Raise Cholesterol Levels

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Regular consumption of milk is not associated with increased levels of cholesterol, according to new research.

A study published in the International Journal of Obesity analysed three large population studies and found that people who regularly drank high amounts of milk had lower levels of both ‘good’ and ‘bad’ cholesterol, although their BMI levels were higher than non-milk drinkers. Analysis of other large studies also suggests that regular milk drinkers had a 14% lower risk of coronary heart disease.

The team of researchers took a genetic approach to milk consumption by looking at a variation in the lactase gene associated with digestion of lactose. The study found that this gene variation for digesting lactose was a good identifier for people who consumed higher levels of milk.

“We found that among participants with a genetic variation that we associated with higher milk intake, they had higher BMI, body fat, but importantly had lower levels of good and bad cholesterol,” said Vimal Karani, Professor of Nutrigenetics and Nutrigenomics at the University of Reading said. “We also found that those with the genetic variation had a significantly lower risk of coronary heart disease. All of this suggests that reducing the intake of milk might not be necessary for preventing cardiovascular diseases.”

Contradictory research on the effect of high dairy intake and obesity and metabolic disorders was the motivation for the study. To exclude the effects of differences in sampling size, ethnicity and other factors, the team conducted a meta-analysis of data in up to 1.9 million people, including the UK Biobank and used the genetic approach to avoid confounding.

Even though the UK Biobank data showed that those with the lactase gene had an 11% reduced risk of type 2 diabetes, the study did not find a link between higher milk intake and increased likelihood of diabetes or related traits, such as glucose and inflammatory biomarkers.

“The study certainly shows that milk consumption is not a significant issue for cardiovascular disease risk even though there was a small rise in BMI and body fat among milk drinkers. What we do note in the study is that it remains unclear whether it is the fat content in dairy products that is contributing to the lower cholesterol levels or it is due to an unknown ‘milk factor’,” said Professor Karani.

Source: EurekaAlert

Journal information: Karani Santhanakrishnan Vimaleswaran et al, Evidence for a causal association between milk intake and cardiometabolic disease outcomes using a two-sample Mendelian Randomization analysis in up to 1,904,220 individuals, International Journal of Obesity (2021). DOI: 10.1038/s41366-021-00841-2

‘Lab Leak’ Theory Gains Ground with Report of Sick Wuhan Lab Staff in 2019

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As reported by the Wall Street Journal, US intelligence learned three doctors at Wuhan Institute of Virology became sick with COVID-like symptoms in November 2019 and sought out hospital care. This, along with an open letter in the journal Science has prompted new calls to find out whether COVID started at that facility. 

A State Department report was issued during the last days of former President Donald Trump’s administration but officials familiar with the report did not agree on the strength of the evidence found, the Journal reported. However this new report adds more detail, and comes on the eve of a World Health Organization meeting, which will no doubt include COVID.

In March, virologist Marion Koopmans told NBC News that the illness of lab workers could be due to normal seasonal illnesses.

Earlier this year, a team from the WHO spent a month in Wuhan investigating the origin of the virus, and produced a report concluding that the virus most likely jumped from bats to people, rating a lab leak as “extremely unlikely”.

The WHO however also said it also did not have access to all the necessary information – a situation has prompted some experts to be wary of the findings and demand more investigations into the virus’s origin, including the possibility that it in fact was leaked from a lab.

November 2019 is also in line with when experts believe COVID began circulating.

For its own part, China has consistently denied that the coronavirus escaped from a lab. However, the lab has not made available its raw data or records on its work with coronaviruses in bats.

A spokeswoman for the National Security Council told the Wall Street Journal that the Biden administration has questions about the virus’, but plausible theories should be investigated by WHO.

“We’re not going to make pronouncements that prejudge an ongoing WHO study into the source of SARS-CoV-2,” the spokeswoman said. “As a matter of policy we never comment on intelligence issues.”

Source: Business Insider

Lockdowns Loom as COVID Spreads Again in SA Provinces

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The Western Cape provincial government has said it is actively preparing for a resurgence of COVID cases while three other provinces have now declared they are in a third wave.

The province’s premier Alan Winde said in a statement on Sunday that based on current trajectories, the province is likely to officially enter its third wave two to three weeks from now.

Gauteng premier David Makhura confirmed that his province officially entered into a third wave more than a week ago. This was followed by similar declarations in the Free State and the Eastern Cape.

“The Western Cape is currently facing a resurgence as it has seen increases in its case numbers every day, over the past 12 days. While this is not yet a third wave, it is the first sign that we are moving towards one,” Winde said.

“Our guiding principle remains that no person will be denied access to life-saving medical treatment. We must make sure we have enough beds, staff and oxygen to respond effectively in the month ahead.”

He added that in the meantime South Africans should continue to follow the level 1 lockdown restrictions, adhering to social distancing and avoid social gatherings to help flatten this curve. But health experts have warned that the rise in cases could require further lockdown restrictions.

Head of the Western Cape Health Department Dr Keith Cloete told EWN that it is a national competency to put lockdown restrictions in place, but they are highly likely to appear given that the number of cases is on the increase countrywide.

Health minister Dr Zweli Mkhize has likewise warned of likely additional restrictions in South Africa due to rising COVID numbers.

He said that the government has discussed the rising numbers. “At some point we are going to have to start looking at additional restrictions,” he said.

“We are going to be recommending that there should be more focus on the size of gatherings, and look at the focus on some of the measures that were actually released when we thought the situation was much more improved.”

He highlighted the importance of trying to maintain a balance to ensure that people continue to be able to work. “We do need to send a strong message still, that people can’t be complacent.”

As of 23 May, there were 2894 new cases in South Africa and the COVID test positive rate stood at 9.86%. Data collected up to 15 May showed the highest positive rate was in the Northern Cape (24.1%), Free State (17.5%) and North West (15.1%) provinces. The percentage testing positive was <10% in all other provinces. (Source: NICD PDF, note this is a 10 MB size)

Source: BusinessTech