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Successful tests in animal models pave way for strategy for universal flu vaccine

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An experimental mRNA-based vaccine against all 20 known subtypes of influenza virus provided broad protection from otherwise lethal flu strains in initial tests, according to a study.

This could serve one day as a general preventative measure against future flu pandemics, the researchers from University of Pennsylvania, US, said.

According to the study, tests in animal models showed that the vaccine dramatically reduced signs of illness and protected from death, even when the animals were exposed to flu strains different from those used in making the vaccine.

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The “multivalent” vaccine, which the researchers described in a paper published in the journal Science, used the same messenger ribonucleic acid (mRNA) technology employed in the Pfizer and Moderna SARS-CoV-2 vaccines, the study said.

This mRNA technology that enabled those Covid-19 vaccines was pioneered at Penn, the study said.

“The idea here is to have a vaccine that will give people a baseline level of immune memory to diverse flu strains, so that there will be far less disease and death when the next flu pandemic occurs,” said study senior author Scott Hensley.

Influenza viruses periodically cause pandemics with enormous death tolls. The best known of these was the 1918-19 “Spanish flu” pandemic, which killed at least tens of millions of people worldwide.

Flu viruses can circulate in birds, pigs, and other animals, and pandemics can start when one of these strains jumps to humans and acquires mutations that adapt it better for spreading among humans.

Current flu vaccines are merely “seasonal” vaccines that protect against recently circulating strains, but would not be expected to protect against new, pandemic strains. The strategy employed by the Penn researchers is to vaccinate using immunogens – a type of antigen that stimulates immune responses – from all known influenza subtypes in order to elicit broad protection, the study said.

The vaccine is not expected to provide “sterilizing” immunity that completely prevents viral infections. Instead, the new study showed that the vaccine elicited a memory immune response that can be quickly recalled and adapted to new pandemic viral strains, significantly reducing severe illness and death from infections.

“It would be comparable to first-generation SARS-CoV-2 mRNA vaccines, which were targeted to the original Wuhan strain of the coronavirus.

“Against later variants such as Omicron, these original vaccines did not fully block viral infections, but they continue to provide durable protection against severe disease and death,” said Hensley.

The experimental vaccine, when injected and taken up by the cells of recipients, started producing copies of a key flu virus protein, the hemagglutinin protein, for all twenty influenza hemagglutinin subtypes—H1 through H18 for influenza A viruses, and two more for influenza B viruses.

“For a conventional vaccine, immunizing against all these subtypes would be a major challenge, but with mRNA technology it’s relatively easy,” Hensley said.

In mice, the mRNA vaccine elicited high levels of antibodies, which stayed elevated for at least four months, and reacted strongly to all 20 flu subtypes. Moreover, the vaccine seemed relatively unaffected by prior influenza virus exposures, which can skew immune responses to conventional influenza vaccines.

The researchers observed that the antibody response in the mice was strong and broad, whether or not the animals had been exposed to flu virus before.

Hensley and his colleagues currently are designing human clinical trials, he said. The researchers envision that, if those trials are successful, the vaccine may be useful for eliciting long-term immune memory against all influenza subtypes in people of all age groups, including young children.

“We think this vaccine could significantly reduce the chances of ever getting a severe flu infection,” Hensley said.

In principle, he added, the same multivalent mRNA strategy can be used for other viruses with pandemic potential, including coronaviruses.

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Ultra-Processed Foods May Be Linked to Increased Risk of Cancer

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Summary: High consumption of ultra-processed foods, including soda, chips, and some white bread products, was associated with an increased risk of developing and dying from certain kinds of cancer, including brain cancer.

Source: Imperial College London

Higher consumption of ultra-processed foods may be linked to an increased risk of developing and dying from cancer, an Imperial College London-led observational study suggests.

Researchers from Imperial’s School of Public Health have produced the most comprehensive assessment to date of the association between ultra-processed foods and the risk of developing cancers.

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Ultra-processed foods are food items which have been heavily processed during their production, such as fizzy drinks, mass-produced packaged breads, many ready meals and most breakfast cereals.

Ultra-processed foods are often relatively cheap, convenient, and heavily marketed, often as healthy options. But these foods are also generally higher in salt, fat, sugar, and contain artificial additives. It is now well documented that they are linked with a range of poor health outcomes including obesity, type 2 diabetes and cardiovascular disease.

The first UK study of its kind used UK Biobank records to collect information on the diets of 200,000 middle-aged adult participants. Researchers monitored participants’ health over a 10-year period, looking at the risk of developing any cancer overall as well as the specific risk of developing 34 types of cancer. They also looked at the risk of people dying from cancer.

The study found that higher consumption of ultra-processed foods was associated with a greater risk of developing cancer overall, and specifically with ovarian and brain cancers. It was also associated with an increased risk of dying from cancer, most notably with ovarian and breast cancers.

For every 10 percent increase in ultra-processed food in a person’s diet, there was an increased incidence of 2 percent for cancer overall, and a 19 percent increase for ovarian cancer specifically.

Each 10 percent increase in ultra-processed food consumption was also associated with increased mortality for cancer overall by 6 percent, alongside a 16 percent increase for breast cancer and a 30 percent increase for ovarian cancer.

These links remained after adjusting for a range of socio-economic, behavioral and dietary factors, such as smoking status, physical activity and body mass index (BMI).

The Imperial team carried out the study, which is published in eClinicalMedicine, in collaboration with researchers from the International Agency for Research on Cancer (IARC), University of São Paulo, and NOVA University Lisbon.

Previous research from the team reported the levels of consumption of ultra-processed foods in the UK, which are the highest in Europe for both adults and children. The team also found that higher consumption of ultra-processed foods was associated with a greater risk of developing obesity and type 2 diabetes in UK adults, and a greater weight gain in UK children extending from childhood to young adulthood.

Dr. Eszter Vamos, lead senior author for the study, from Imperial College London’s School of Public Health, said, “This study adds to the growing evidence that ultra-processed foods are likely to negatively impact our health including our risk for cancer. Given the high levels of consumption in UK adults and children, this has important implications for future health outcomes.

“Although our study cannot prove causation, other available evidence shows that reducing ultra-processed foods in our diet could provide important health benefits. Further research is needed to confirm these findings and understand the best public health strategies to reduce the widespread presence and harms of ultra-processed foods in our diet.”

Dr. Kiara Chang, first author for the study, from Imperial College London’s School of Public Health, said, “The average person in the UK consumes more than half of their daily energy intake from ultra-processed foods.

“This is exceptionally high and concerning as ultra-processed foods are produced with industrially derived ingredients and often use food additives to adjust color, flavor, consistency, texture, or extend shelf life.

See also

This shows chips
The study found that higher consumption of ultra-processed foods was associated with a greater risk of developing cancer overall, and specifically with ovarian and brain cancers. Image is in the public domain

“Our bodies may not react the same way to these ultra-processed ingredients and additives as they do to fresh and nutritious minimally processed foods. However, ultra-processed foods are everywhere and highly marketed with cheap price and attractive packaging to promote consumption. This shows our food environment needs urgent reform to protect the population from ultra-processed foods.”

The World Health Organization and the United Nations’ Food and Agriculture Organization has previously recommended restricting ultra-processed foods as part of a healthy sustainable diet.

There are ongoing efforts to reduce ultra-processed food consumption around the world, with countries such as Brazil, France and Canada updating their national dietary guidelines with recommendations to limit such foods. Brazil has also banned the marketing of ultra-processed foods in schools. There are currently no similar measures to tackle ultra-processed foods in the UK.

Dr. Chang added, “We need clear front of pack warning labels for ultra-processed foods to aid consumer choices, and our sugar tax should be extended to cover ultra-processed fizzy drinks, fruit-based and milk-based drinks, as well as other ultra-processed products.

“Lower income households are particularly vulnerable to these cheap and unhealthy ultra-processed foods. Minimally processed and freshly prepared meals should be subsidized to ensure everyone has access to healthy, nutritious and affordable options.”

The researchers note that their study is observational, so does not show a causal link between ultra-processed foods and cancer due to the observational nature of the research. More work is needed in this area to establish a causal link.

About this diet and brain cancer research news

Author: Press Office
Source: Imperial College London
Contact: Press Office – Imperial College London
Image: The image is in the public domain

Original Research: The findings will appear in eClinicalMedicine

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ER closure for Seaforth’s emergency department due to COVID-19 outbreak

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Starting on Feb. 1, Seaforth’s emergency department will be closed in the overnight hours.

The Huron Perth Healthcare Alliance said due to “sudden health human resource shortages related to COVID-19,” the Seaforth Community Hospital’s emergency department will be closed from 5 p.m. to 7 a.m., from Feb. 1st to Feb. 6, when regular hours are expected to resume.

On Jan. 28, a COVID-19 outbreak was declared in Seaforth’s inpatient unit, closing all admissions to the unit. On Tuesday, a COVID-19 outbreak was declared at the Clinton General Hospital’s inpatient unit, also closing it to admissions.

In total, 10 people are in Huron-Perth hospitals dealing with COVID-19.

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Two long-term care homes in the region are also dealing with COVID-19 outbreaks at the moment. Since Jan. 1, eight Huron-Perth residents, most of them over the age of 75, have died due to COVID-19, according to the Huron Perth Health Unit.

“I extend my condolences to the loved ones of these individuals,” said Dr. Miriam Klassen, medical officer of health for the Huron Perth Health Unit.

She added, “COVID-19 remains a serious illness for some people, especially those who are older. While we are seeing signs of improvement, it is important to keep taking actions to protect those who are most vulnerable to severe outcomes from this virus.”

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GLP-1 Agonists Protected Kidneys in T2D With Advanced DKD

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Researchers published the study covered in this summary on Research Square as a preprint that has not yet been peer reviewed.

Key Takeaways

  • In patients with advanced diabetic kidney disease (DKD; estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73m2), treatment with a glucagon-like peptide-1 (GLP-1) agonist had a neutral effect on cardiovascular outcomes but significantly linked with preservation of kidney function and improved survival in a propensity-score matched, retrospective analysis of observational data from more than 2000 people with type 2 diabetes in Taiwan.

Why This Matters

  • Cardiovascular disease is a leading cause of mortality in people with type 2 diabetes and among those with chronic kidney disease.
  • GLP-1 agonists reduce all-cause mortality and cardiovascular death in people with type 2 diabetes, but their role in patients with advanced DKD is controversial.
  • Research on the effect of GLP-1 agonists on cardiovascular outcomes in patients with advanced DKD is limited. Trials that have assessed GLP-1 agonists in people with type 2 diabetes have generally excluded those with advanced DKD and completely excluded those with end-stage kidney disease (eGFR < 30 mL/min/1.73m2).
  • Treatment with GLP-1 agonists has been associated with a significant reduction in composite cardiovascular outcomes in people with type 2 diabetes and relatively fair kidney function (eGFR > 30 mL/min/1.73m2), but among people with type 2 diabetes and lower levels of kidney function, research has shown neutral composite cardiovascular outcomes levels. However, limitations of previous studies include being mainly based on subgroup analysis or including a limited sample of patients.

Study Design

  • Retrospective analysis of observational data from nearly 9000 people in Taiwan with type 2 diabetes and an eGFR < 30 mL/min/1.73m2 who received a first prescription for a GLP-1 agonist or dipeptidyl peptidase 4 (DPP-4) inhibitor in 2012-2021 and had the data necessary for this analysis in their records.
  • The data came from the largest multi-institutional electronic medical record database in Taiwan, which includes two medical centers and five general hospitals and information on more than 11 million patients, from 2001 to 2019.
  • Researchers used propensity scoring to match 602 people treated with a GLP-1 agonist with 1479 people treated with a DPP-4 inhibitor.

Key Results

  • During a mean follow-up of 2.1 years, the rate of the composite cardiovascular outcome (cardiovascular death, myocardial infarction, and ischemic stroke) did not significantly differ between the GLP-1 agonist and DPP-4 inhibitor groups, with incidence rates of 13.0% and 13.8%, respectively, and a nonsignificant hazard ratio of 0.88. Rates of each of the three components of the composite endpoint also did not significantly differ between the two groups.
  • Progression to end-stage kidney disease with dialysis was significantly lower in those treated with a GLP-1 agonist compared with a DPP-4 inhibitor, with incidence rates of 23.4% and 27.5%, respectively, and a significant hazard ratio of 0.72.
  • The incidence of a greater than 50% drop in eGFR from baseline was 32.2% with GLP-1 agonist treatment compared to 35.9% with a DPP-4 inhibitor, with a significant hazard ratio of 0.74.
  • Median time until patients needed new-onset dialysis was 1.9 years with GLP-1 agonist treatment and 1.3 years with DPP-4 inhibitor treatment, which was a significant difference.
  • The rate of all-cause death was 18.4% with GLP-1 agonist treatment compared with 25.1% with DPP-4 inhibitor treatment, a hazard ratio of 0.71 that was significant.

Limitations

  • Because the study was a retrospective analysis of observational data it cannot prove causality.
  • The study could be subject to residual confounding despite propensity-score matching.
  • The data came from health records that could have included coding errors.
  • Treatment compliance was unknown.

Disclosures

This is a summary of a preprint research study, “The cardiovascular and renal effects of glucagon-like peptide 1 receptor agonists in patients with advanced diabetic kidney disease,” by researchers in Taiwan on Research Square and provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on researchsquare.com.

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