Summer Sweets

Mango Cakes and Parfait

Melon Cakes and Parfait

Traditional Nyonya Lapis

Ingredients

375 g butter
170 g sugar
1/2 tin condensed milk
2 tbsps Brandy
18 egg yolks
6 egg whites
110 g all-purpose flour
1/2 tsp cream of tartar
1 tsp mixed spice

Method

  1. Sift flour and mix it with mixed spice.
  2. Cream butter together with condensed milk until creamy.
  3. Whisk egg yolks with 100 g sugar till thick.
  4. Add the remaining sugar and 1/2 tsp of cream of tartar to egg whites. Use high speed to beat up the egg whites till stiff.
  5. Fold in alternately the egg yolk mixture and the egg white mixture to the creamed butter while adding a little of flour at a time. Lastly add in the brandy.
  6. Grease on the bottom and sides of a 9-inch square tray. Place a piece of 9-inch square greaseproof paper to fit the base of the tin and grease again with butter.
  7. Preheat oven’s upper element at 200°C. Place greased tray under grill for 1 minute.
  8. Pour 3 tbsps of the batter into the tray and spread mixture evenly. Bake for 5 – 7 minutes or till light brown.
  9. Remove tray from grill. Use a skewer or toothpick to prick holes on top of cake to prevent air bubbles from forming. Repeat this step layer by layer till mixture is used up. Unmould cake at once. Turn it over on a cooling rack to cool for 1 hour.

Source: Delicious Nyonya Kueh and Dessert

Study: Malaria Drug Hydroxychloroquine Fails to Prevent COVID-19

Michael Erman wrote . . . . . . . . .

The malaria drug promoted by U.S. President Donald Trump as a treatment for COVID-19 was ineffective in preventing infection in people exposed to the coronavirus, according to a widely anticipated clinical trial released on Wednesday.

The new trial found no serious side effects or heart problems from use of hydroxychloroquine.

Vocal support from Trump kicked off a heated debate and raised expectations for the decades-old drug that could be a cheap and widely available tool in fighting the pandemic that has infected more than 6.4 million people and killed over 382,000 worldwide

In the first major study comparing hydroxychloroquine to a placebo to gauge its effect against the new coronavirus, University of Minnesota researchers tested 821 people who had recently been exposed to the virus or lived in a high-risk household.

It found 11.8% of subjects given hydroxychloroquine developed symptoms compatible with COVID-19, compared with 14.3%who got a placebo. That difference was not statistically significant, meaning the drug was no better than placebo.

“Our data is pretty clear that for post exposure, this does not really work,” said Dr. David Boulware, the trial’s lead researcher and an infectious disease physician at the University of Minnesota.

Several trials of the drug have been stopped over concerns about its safety for treating COVID-19 that were raised by health regulators and previous less rigorous studies.

“I think both sides – one side who is saying ‘this is a dangerous drug’ and the other side that says ‘this works’ – neither is correct,” said Boulware.

The results were also published in the New England Journal of Medicine.

In March, Trump said hydroxychloroquine used in combination with the antibiotic azithromycin had “a real chance to be one of the biggest game changers in the history of medicine” with little evidence to back up that claim. He later said he took the drugs preventively after two people who worked at the White House were diagnosed with COVID-19, the illness caused by the novel coronavirus.

Hydroxychloroquine – which has anti-inflammatory and antiviral properties – inhibited the virus in laboratory experiments. But these type of human trials are needed to definitively demonstrate whether the drug’s benefits, if any, outweigh the risks when compared with a placebo.

Proponents of the drug as a COVID-19 treatment argue it may need to be administered at an earlier stage in the disease to be effective. Others have suggested that it needs to be used in combination with the mineral zinc, which can help boost the immune system.

More than 20% of the trial subjects also took zinc, which had no significant effect.

The U.S. Food and Drug Administration cautioned in late April against the use of hydroxychloroquine in patients with heart disease due to an increased risk of dangerous cardiac rhythm problems.

Boulware said his trial had fewer participants than initially planned because of difficulty enrolling new subjects after the FDA’s warning.

On Tuesday, the British medical journal the Lancet said it had concerns about data behind an influential article that found hydroxychloroquine increased the risk of death in COVID-19 patients, a conclusion that undercut scientific interest in the medicine.

Boulware was one of the signatories of an open letter from doctors that called attention to potential problems with that study.

Some European governments banned hydroxychloroquine for COVID-19 patients, and U.S. hospitals have significantly cut back its use.

In the University of Minnesota trial, 40% of the those who took hydroxychloroquine reported less serious side effects like nausea and abdominal discomfort versus 17% in the placebo group.

Results of another University of Minnesota placebo-controlled trial testing hydroxychloroquine as a coronavirus treatment rather than to prevent infection is expected soon.

Source: Reuters

Researchers Develops ‘Poisoned Arrow’ to Defeat Antibiotic-resistant Bacteria

Liz Fuller-Wright wrote . . . . . . . . .

A team of Princeton researchers reported today in the journal Cell that they have found a compound, SCH-79797, that can simultaneously puncture bacterial walls and destroy folate within their cells — while being immune to antibiotic resistance.

Bacterial infections come in two flavors — Gram-positive and Gram-negative — named for the scientist who discovered how to distinguish them. The key difference is that Gram-negative bacteria are armored with an outer layer that shrugs off most antibiotics. In fact, no new classes of Gram-negative-killing drugs have come to market in nearly 30 years.

“This is the first antibiotic that can target Gram-positives and Gram-negatives without resistance,” said Zemer Gitai, Princeton’s Edwin Grant Conklin Professor of Biology and the senior author on the paper. “From a ‘Why it’s useful’ perspective, that’s the crux. But what we’re most excited about as scientists is something we’ve discovered about how this antibiotic works — attacking via two different mechanisms within one molecule — that we are hoping is generalizable, leading to better antibiotics — and new types of antibiotics — in the future.”

Gitai poses with James Martin, who led the research team and is first author on the new article about the ‘poisoned arrow’ antibiotic, at Martin’s 2019 Ph.D. thesis defense.

The greatest weakness of antibiotics is that bacteria evolve quickly to resist them, but the Princeton team found that even with extraordinary effort, they were unable to generate any resistance to this compound. “This is really promising, which is why we call the compound’s derivatives ‘Irresistin,’” Gitai said.

It’s the holy grail of antibiotics research: an antibiotic that is effective against diseases and immune to resistance while being safe in humans (unlike rubbing alcohol or bleach, which are irresistibly fatal to human cells and bacterial cells alike).

For an antibiotics researcher, this is like discovering the formula to convert lead to gold, or riding a unicorn — something everyone wants but no one really believes exists, said James Martin, a 2019 Ph.D. graduate who spent most of his graduate career working on this compound. “My first challenge was convincing the lab that it was true,” he said.

But irresistibility is a double-edged sword. Typical antibiotics research involves finding a molecule that can kill bacteria, breeding multiple generations until the bacteria evolve resistance to it, looking at how exactly that resistance operates, and using that to reverse-engineer how the molecule works in the first place.

But since SCH-79797 is irresistible, the researchers had nothing to reverse engineer from.

“This was a real technical feat,” said Gitai. “No resistance is a plus from the usage side, but a challenge from the scientific side.”

The research team had two huge technical challenges: Trying to prove the negative — that nothing can resist SCH-79797 — and then figuring out how the compound works.

To prove its resistance to resistance, Martin tried endless different assays and methods, none of which revealed a particle of resistance to the SCH compound. Finally, he tried brute force: for 25 days, he “serially passaged” it, meaning that he exposed bacteria to the drug over and over and over again. Since bacteria take about 20 minutes per generation, the germs had millions of chances to evolve resistance — but they didn’t. To check their methods, the team also serially passaged other antibiotics (novobiocin, trimethoprim, nisin and gentamicin) and quickly bred resistance to them.

Proving a negative is technically impossible, so the researchers use phrases like “undetectably-low resistance frequencies” and “no detectable resistance,” but the upshot is that SCH-79797 is irresistible — hence the name they gave to its derivative compounds, Irresistin.

They also tried using it against bacterial species that are known for their antibiotic resistance, including Neisseria gonorrhoeae, which is on the top 5 list of urgent threats published by the Center for Disease Control and Prevention.

“Gonorrhea poses a huge problem with respect to multidrug resistance,” said Gitai. “We’ve run out of drugs for gonorrhea. With most common infections, the old-school generic drugs still work. When I got strep throat two years ago, I was given penicillin-G — the penicillin discovered in 1928! But for N. gonorrhoeae, the standard strains that are circulating on college campuses are super drug resistant. What used to be the last line of defense, the break-glass-in-case-of-emergency drug for Neisseria, is now the front-line standard of care, and there really is no break-glass backup anymore. That’s why this one is a particularly important and exciting one that we could cure.”

The researchers even got a sample of the most resistant strain of N. gonorrhoeae from the vaults of the World Health Organization — a strain that is resistant to every known antibiotic — and “Joe showed that our guy still killed this strain,” Gitai said, referring to Joseph Sheehan, a co-first-author on the paper and the lab manager for the Gitai Lab. “We’re pretty excited about that.”

The poison-tipped arrow

Without resistance to reverse engineer from, the researchers spent years trying to determine how the molecule kills bacteria, using a huge array of approaches, from classical techniques that have been around since the discovery of penicillin through to cutting-edge technology.

Martin called it the “everything but the kitchen sink” approach, and it eventually revealed that SCH-79797 uses two distinct mechanisms within one molecule, like an arrow coated in poison.

“The arrow has to be sharp to get the poison in, but the poison has to kill on its own, too,” said Benjamin Bratton, an associate research scholar in molecular biology and a lecturer in the Lewis Sigler Institute for Integrative Genomics, who is the other co-first-author.

The arrow targets the outer membrane — piercing through even the thick armor of Gram-negative bacteria — while the poison shreds folate, a fundamental building block of RNA and DNA. The researchers were surprised to discover that the two mechanisms operate synergistically, combining into more than a sum of their parts.

“If you just take those two halves — there are commercially available drugs that can attack either of those two pathways — and you just dump them into the same pot, that doesn’t kill as effectively as our molecule, which has them joined together on the same body,” Bratton said.

There was one problem: The original SCH-79797 killed human cells and bacterial cells at roughly similar levels, meaning that as a medicine, it ran the risk of killing the patient before it killed the infection. The derivative Irresistin-16 fixed that. It is nearly 1,000 times more potent against bacteria than human cells, making it a promising antibiotic. As a final confirmation, the researchers demonstrated that they could use Irresistin-16 to cure mice infected with N. gonorrhoeae.

New hope

This poisoned arrow paradigm could revolutionize antibiotic development, said KC Huang, a professor of bioengineering and of microbiology and immunology at Stanford University who was not involved in this research.

“The thing that can’t be overstated is that antibiotic research has stalled over a period of many decades,” Huang said. “It’s rare to find a scientific field which is so well studied and yet so in need of a jolt of new energy.”

The poisoned arrow, the synergy between two mechanisms of attacking bacteria, “can provide exactly that,” said Huang, who was a postdoctoral researcher at Princeton from 2004 to 2008. “This compound is already so useful by itself, but also, people can start designing new compounds that are inspired by this. That’s what has made this work so exciting.”

In particular, each of the two mechanisms — the arrow and the poison — target processes that are present in both bacteria and in mammalian cells. Folate is vital to mammals (which is why pregnant women are told to take folic acid), and of course both bacteria and mammalian cells have membranes. “This gives us a lot of hope, because there’s a whole class of targets that people have largely neglected because they thought, ‘Oh, I can’t target that, because then I would just kill the human as well,’” Gitai said.

“A study like this says that we can go back and revisit what we thought were the limitations on our development of new antibiotics,” Huang said. “From a societal point of view, it’s fantastic to have new hope for the future.”

Source: Princeton University

Plasma Therapy Aids Recovery in Critically Ill COVID-19 Patients

Alan Mozes wrote . . . . . . . . .

The blood plasma of people who have recovered from the new coronavirus infection may help critically ill COVID-19 patients recover, a new study finds.

Of 25 sick patients given plasma transfusions, 19 improved and 11 left the hospital, the researchers reported. None of the patients had side effects from the transfusion.

“While physician scientists around the world scrambled to test new drugs and treatments against the COVID-19 virus, convalescent serum therapy emerged as potentially one of the most promising strategies,” explained lead researcher Dr. James Musser, chair of the department of pathology and genomic medicine at Houston Methodist hospital. “With no proven treatments or cures for COVID-19 patients, now was the time in our history to move ahead rapidly.”

Plasma transfusions from recovered patients have been used since at least 1918 during the Spanish Flu pandemic and in 2003 in the SARS (severe acute respiratory syndrome) pandemic. It was also employed in the influenza H1N1 pandemic in 2009 and the 2015 Ebola outbreak in Africa, the researchers noted.

The new report was published online recently in the American Journal of Pathology.

This latest study isn’t the only research looking into the power of plasma transfusions in treating COVID-19.

Two groups of researchers are testing the theory in clinical trials.

One study, from doctors at NYU Grossman School of Medicine, Montefiore Health System and Albert Einstein College of Medicine in New York City, will try to determine whether “convalescent plasma” injected into hospitalized COVID-19 patients can protect them from developing severe disease or requiring a ventilator.

Meanwhile, researchers at the Johns Hopkins Bloomberg School of Public Health in Baltimore are poised to launch a pair of new studies looking at the use of plasma in health care workers and those who are sick at home with COVID-19.

Dr. Corita Grudzen, vice chair for research in NYU Langone Health’s department of emergency medicine, wrote the study protocol for the New York City study.

“What we hope to see is that convalescent plasma, used at this stage of disease, so early on, prevents patients from dying, from going on a mechanical ventilator, or any sort of bad outcome,” Grudzen said in a HealthDay Live interview.

The tactic is “sort of a stopgap measure in the sense that, when you don’t have a vaccine, it’s something that can be used in a new infection where we don’t have known drugs or other therapeutics or biologics that we know can work against the disease,” Grudzen explained.

Exactly what is blood plasma?

“Blood plasma is the liquid part of the blood,” explained Dr. Arturo Casadevall, chair of Hopkins’ department of molecular microbiology and immunology and lead researcher on the two Hopkins studies.

Characterized by its yellowish cast, plasma contains both red and white blood cells, as well as the colorless platelets the body deploys to clot and stem bleeding from wounds or cuts.

“And that’s [also] where the antibodies are,” Casadevall noted. “The antibodies are floating in the liquid.”

With plasma therapy, he explained, “you’re taking the antibodies that somebody else made when they recovered and you’re transferring them to a new person. So, the new person gets them already made, and can use them right away.”

Convalescent plasma is not without dangers.

The two main ones are the patient catching an infectious disease, though blood screening helps to lessen that possibility, or a patient’s immune system reacting badly to the injected plasma of another person. Grudzen noted that, “especially in older people, it’s a little more risky.”

And Casadevall cautioned that plasma therapy still needs to be tested on COVID-19 to see if it’ll work against this specific virus, “simply because it’s a new organism.”

To that end, Hopkins is set to start two COVID-19 plasma investigations simultaneously, with funding coming from Bloomberg Philanthropies, the state of Maryland, and Hopkins.

“The first trial is focused on trying to use plasma on high-risk populations,” he noted. That investigation will include health care workers on the frontlines of the pandemic and nursing home residents, with a minimum of 150 participants.

“The second trial is focused on people who are sick at home,” Casadevall said. “We know most people recover. Most people today who are sick are sitting at home hoping to get better. But we also know that some fraction of them will get worse,” he added.

Source: HealthDay


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