High-protein diets clog arteries, up heart disease risk

Agencies
January 26, 2020

High-protein diets may help people lose weight and build muscle, but there is a downside to it --a greater heart attack risk. Researchers now report that high-protein diets boost artery-clogging plaque.

The research in mice showed that high-protein diets spur unstable plaque -- the kind most prone to rupturing and causing blocked arteries.

More plaque buildup in the arteries, particularly if it's unstable, increases the risk of heart attack.

"There are clear weight-loss benefits to high-protein diets, which has boosted their popularity in recent years," said senior author Babak Razani, associate professor at Washington University School of Medicine in St. Louis, Missouri.

"But animal studies and some large epidemiological studies in people have linked high dietary protein to cardiovascular problems. We decided to take a look at whether there is truly a causal link between high dietary protein and poorer cardiovascular health," Razani added.

The researchers studied mice who were fed a high-fat diet to deliberately induce atherosclerosis, or plaque buildup in the arteries.

Some of the mice received a high-fat diet that was also high in protein. And others were fed a high-fat, low-protein diet for comparison.

The mice on the high-fat, high-protein diet developed worse atherosclerosis -- about 30 per cent more plaque in the arteries -- than mice on the high-fat, normal-protein diet, despite the fact that the mice eating more protein did not gain weight, unlike the mice on the high-fat, normal-protein diet.

"A couple of a scoop of protein powder in a milkshake or smoothie adds something like 40 grams of protein -- almost equivalent to the daily recommended intake," Razani said.

"To see if protein has an effect on cardiovascular health, we tripled the amount of protein that the mice receive in the high-fat, high-protein diet -- keeping the fat constant. Protein went from 15 per cent to 46 per cent of calories for these mice".

Plaque contains a mix of fat, cholesterol, calcium deposits and dead cells. Past work by Razani's team and other groups has shown that immune cells called macrophages work to clean up plaque in the arteries.

But the environment inside plaque can overwhelm these cells, and when such cells die, they make the problem worse, contributing to plaque buildup and increasing plaque complexity.

"In mice on the high-protein diet, their plaques were a macrophage graveyard," Razani informed.

To understand how high dietary protein might increase plaque complexity, Razani and his colleagues also studied the path protein takes after it has been digested -- broken down into its original building blocks, called amino acids.

"This study is not the first to show a telltale increase in plaque with high-protein diets, but it offers a deeper understanding of the impact of high protein with the detailed analysis of the plaques," said Razani.

"This work not only defines the critical processes underlying the cardiovascular risks of dietary protein but also lays the groundwork for targeting these pathways in treating heart disease," he added.

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Agencies
July 2,2020

The American pharmaceutical giant Pfizer Inc. and the European biotechnology company BioNTech SE have conducted an experimental trial of a COVID-19 vaccine candidate and found it to be safe, well-tolerated, and capable of generating antibodies in the patients.

The study, which is yet to be peer-reviewed, describes the preliminary clinical data for the candidate vaccine -- nucleoside-modified messenger RNA (modRNA), BNT162b1.

It said the amount of antibodies produced in participants after they received two shots of the vaccine candidate was greater than that reported in patients receiving convalescent plasma from recovered COVID-19 patients.

"I was glad to see Pfizer put up their phase 1 trial data today. Virus neutralizing antibody titers achieved after two doses are greater than convalescent antibody titers," tweeted Peter Hotez, a vaccine scientist from Baylor College of Medicine in the US, who was unrelated to the study.

Researchers, including those from New York University in the US, who were involved in the study, said the candidate vaccine enables human cells to produce an optimised version of the receptor binding domain (RBD) antigen -- a part of the spike (S) protein of SARS-CoV-2 which it uses to gain entry into human cells.

"Robust immunogenicity was observed after vaccination with BNT162b1," the scientists noted in the study.

They said the program is evaluating at least four experimental vaccines, each of which represents a unique combination of mRNA format and target component of the novel coronavirus, SARS-CoV-2.

Based on the study's findings, they said BNT162b1 could be administered in a quantity that was well tolerated, potentially generating a dose dependent production of immune system molecules in the patients.

The research noted that patients treated with the vaccine candidate produced nearly 1.8 to 2.8 fold greater levels of RBD-binding antibodies that could neutralise SARS-CoV-2.

"We are encouraged by the clinical data of BNT162b1, one of four mRNA constructs we are evaluating clinically, and for which we have positive, preliminary, topline findings," said Kathrin U. Jansen, study co-author and Senior Vice President and Head of Vaccine Research & Development, Pfizer.

"We look forward to publishing our clinical data in a peer-reviewed journal as quickly as possible," Jansen said.

According to Ugur Sahin, CEO and Co-founder of BioNTech, and another co-author of the study, the preliminary data are encouraging as they provide an initial signal that BNT162b1 is able to produce neutralising antibody responses in humans.

He said the immune response observed in the patients treated with the experimental vaccine are at, or above, the levels observed from convalescent sera, adding that it does so at "relatively low dose levels."

"We look forward to providing further data updates on BNT162b1," Sahin said.

According to a statement from Pfizer, the initial part of the study included 45 healthy adults 18 to 55 years of age.

It said the priliminary data for BNT162b1 was evaluated in 24 subjects who received two injections of 10 microgrammes ( g) and 30 g -- 12 subjects who received a single injection of 100 g, and 9 subjects who received two doses of a dummy vaccine.

The study noted that participants received two doses, 21 days apart, of placebo, 10 g or 30 g of BNT162b1, or received a single dose of 100 g of the vaccine candidate.

According to the scientists, the highest neutralising concentrations of antibodies were observed seven days after the second dose of 10 g, or 30 g on day 28 after vaccination.

They said the neutralising concentrations were 1.8- and 2.8-times that observed in a panel of 38 blood samples from people who had contracted the virus.

In all 24 subjects who received two vaccinations at 10 g and 30 g dose levels, elevation of RBD-binding antibody concentrations was observed after the second injection, the study noted.

It said these concentrations are 8- and 46.3-times the concentration seen in a panel of 38 blood samples from those infected with the novel coronavirus.

At the 10 g or 30 g dose levels, the scientists said adverse reactions, including low grade fever, were more common after the second dose than the first dose.

According to Pfizer, local reactions and systemic events after injection with 10 g and 30 g of BNT162b1 were "dose-dependent, generally mild to moderate, and transient."

It said the most commonly reported local reaction was injection site pain, which was mild to moderate, except in one of 12 subjects who received a 100 g dose, which was severe.

The study noted that there was no serious adverse events reported by the patients.

Citing the limitations of the research, the scientists said the immunity generated in the participants in the form of the T cells and B cells of their immune system, and the level of immunity needed to protect one from COVID-19 are unknown.

With these preliminary data, along with additional data being generated, Pfizer noted in the statement that the two companies will determine a dose level, and select among multiple vaccine candidates to seek to progress to a large, global safety and efficacy trial, which may involve up to 30,000 healthy participants if regulatory approval to proceed is received.

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Agencies
June 17,2020

Leading physicians are celebrating a small dose of good news that arrived Tuesday about dexamethasone, a cheap and widely used steroid shown to be able to save lives among COVID-19 patients, but also cautioning against releasing study results by press release during a global health emergency, like in the case of the latest dexamethasone study by University of Oxford.

"It will be great news if dexamethasone, a cheap steroid, really does cut deaths by one-third in ventilated patients with COVID19, but after all the retractions and walk backs, it is unacceptable to tout study results by press release without releasing the paper", Atul Gawande, surgeon and CEO of Haven Healthcare, tweeted.

"Bottom line is, good news," Dr. Fauci, America's foremost infectious diseases expert told a US newswire on Tuesday, soon after the dexamethasone results were announced in the UK.

Fauci, who has long championed the therapeutics-first view said that dexamethasone is a "significant improvement" in the available therapeutic options currently available.

On Medical Twitter and Facebook, doctors broadly agree that dexamethasone use aligns well with the way COVID19 attacks the body's immune system. Fauci said the results in the Oxford study make "perfect sense" in that context.

"We should see the number of people who actually survive go up, if the study holds up," virologist and epidemiologist Dr. Joseph Fair told a television network.

Global coronavirus cases crossed 8 million on Tuesday. In the US, Texas and Florida are facing a new wave of cases after lifting lockdown orders earlier than medical experts recommended. Amidst the relentless graph upwards, the dexamethasone study results injected hope for better survival rates among those most seriously ill.

World Health Organization chief scientist Soumya Swaminathan welcomed the results from the randomised control trial.

Dr Eugene Gu, Founder and CEO of CoolQuit tweeted that he is "genuinely impressed" with the UK dexamethasone trial. This may be a "game changer", he wrote.

"There's no conflict of interest as dexamethasone is a generic steroid. The mechanism of action makes sense because steroids can reduce cytokine storms and overactive immune systems that makes COVID-19 so deadly. The number needed to treat is 8 ventilated patients which is great."

The Oxford study found that dexamethasone reduced deaths by 35 percent in patients who needed treatment with breathing machines and by 20 percent in those only needing supplemental oxygen. Dexamethasone was one of 5 drugs studied in a large clinical trial in the United Kingdom named RECOVERY, short for Randomised Evaluation of COVID-19 Therapy.

Peter Horby, chief investigator of the University of Oxford clinical trial, said dexamethasone is the first drug to be shown to improve survival in COVID-19. Details of the study have not been released. The trial organisers said they made their announcement via a news release because of "the public health importance of these results." According to Horby's public comments, there was a lot of initial resistance to studying steroids.

During the study, 2,104 patients were randomly selected to be given 6 milligrams of dexamethasone once a day (either by mouth or by intravenous injection) for 10 days. That group was compared with 4,321 patients who received the usual care alone.

Researchers estimated that dexamethasone would prevent one death for every eight patients treated while on ventilators and one for every 25 patients on extra oxygen alone.

UK experts have called the study results a breakthrough in the fight against the virus. The researchers have promised they would publish the results soon.

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Agencies
February 11,2020

Using smartphone for long hours every day may do you more harm than you can probably think of. Researchers have found that spending a lot of time with the device and on social media may lead to mental distress and suicidality among adolescents.

The findings, published in the journal CMAJ (Canadian Medical Association Journal) contains guidance for physicians, parents and teachers on how to help teenagers manage smartphone and social media use for a healthy balance between sleep, academic work, social activity, interpersonal relationships and online activity.

"Physicians, teachers and families need to work together with youth to decrease possible harmful effects of smartphones and social media on their relationships, sense of self, sleep, academic performance, and emotional well-being," said lead author of the study Elia Abi-Jaoude from Toronto Western Hospital in Canada.

This review of evidence, led by the Hospital for Sick Children (SickKids), focuses on smartphone use and does not consider online gaming.

"For adolescents today, who have not known a world without social media, digital interactions are the norm, and the potential benefits of online access to productive mental health information -- including media literacy, creativity, self-expression, sense of belonging and civic engagement -- as well as low barriers to resources such as crisis lines and Internet-based talking therapies cannot be discounted," the authors wrote.

The researchers recommend that doctors should ask teenagers to reduce social media use rather than eradicate it completely and encourage parents to be part of the conversations.

Parents should discuss appropriate smartphone use with teenagers to determine together how to reduce risks and set boundaries.

A recent poll from the US indicates that 54 per cent of teenagers think they spend too much time on their smartphones and about half said they were cutting back on usage.

"Encouragingly, youth are increasingly recognising the negative impact of social media on their lives and starting to take steps to mitigate it," the authors wrote.

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