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Could a single synthetic molecule outsmart a variety of drug-resistant bacteria?

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Could a single synthetic molecule outsmart a variety of drug-resistant bacteria?

An estimated 2.8 million people in the U.S. contract infections each year from bacteria resistant to antibiotics, according to the U.S. Centers for Disease Control. More than 35,000 of them die.

Despite the mounting toll — and the prospect of an eventual surge in superbug fatalities — the development of new antibiotics has failed to keep pace with the threat. A new medicine capable of combating Gram-negative bacteria, a particularly hardy type of bug with inner and outer membranes that antibiotics struggle to cross, hasn’t hit the market in 50 years.

So when a new substance appears on the scene with a decent chance of eventually becoming one of these desperately-needed drugs, scientists say it’s a big deal.

Researchers at Harvard and the University of Illinois at Chicago have created a new molecule that effectively vanquished multiple types of bacteria when tested in animals. The organisms on its hit list included strains of Staphylococcus aureus, Escherichia coli and other pathogens that have become resistant to most antibiotics currently available.

The new molecule, dubbed cresomycin, was described Thursday in the journal Science.

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Cresomycin is not yet a drug, nor is it close to being ready for clinical trials in humans. But it represents a promising enough step toward new treatments that a nonprofit dedicated to fighting superbugs gave its Harvard creator $1.2 million this week to develop cresomycin and similar substances into new oral antibiotics.

“I’ve never been more optimistic or excited about a project,” said Andrew Myers, the Harvard University chemist whose lab developed the molecule.

Cresomycin belongs to a class of antibiotics known as enhanced lincosamides. It works by targeting a bacterium’s ribosome, the tiny protein factory tucked in every living cell.

“Ribosomes can be viewed as a molecular 3-D printer,” said Yury Polikanov, a structural biologist at the University of Illinois at Chicago and a co-author of the paper.

Just as those machines take plastic molecules and use them to construct objects of any shape, ribosomes take genetic information from RNA and use it to crank out proteins.

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Since proteins are essential to virtually all cellular activity, ribosomes are vital to bacteria. That’s why many antibiotics are designed to target them.

But bacteria are always evolving — and embracing new adaptations that help them thwart our attempts to kill them. In some cases, bacteria do this by inserting a tiny chemical dab known as a methyl group into its ribosome. When an antibiotic attempts to bind to the ribosome, that methyl group repels it.

The methyl group acts like a tiny thumbtack set out on the seat the antibiotic was hoping to take, Polikanov said.

“Not very comfortable to sit when a needle is poking you,” he said.

But unlike previous antibiotics, cresomycin binds so tightly to the ribosome that it essentially negates the effect of the methyl group.

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Returning to the thumbtack analogy, Polikanov said the molecule sits on its ribosome seat with such force that it drives the tack into the chair. The ribosome’s best defense is neutralized, allowing cresomycin to get on with its bacteria-killing work.

In test tubes, cresomycin proved much more effective than currently available antibiotics at inhibiting the growth of several types of bacteria. These included a nasty bug called carbapenem-resistant Acinetobacter baumannii that tends to show up in hospitals, E. coli and Neisseria gonorrhoeae, the bacteria that causes gonorrhea.

Researchers then took 20 mice and deliberately infected them with methicillin-resistant S. aureus, better known as MRSA. Half the mice were given four injections of cresomycin over the course of a day, and the other half received injections without the active ingredient.

All but one of the mice who didn’t get treatment were dead two days later. In contrast, all 10 of the mice who received cresomycin were still alive seven days after treatment.

In the Science paper, the authors were quick to note that cresomycin is not yet ready for clinical trials in humans.

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The Harvard lab manufactured more than 60 molecules in its quest for one as effective as cresomycin, and that presents just a tiny fraction of the “exponentially greater numbers” of possible variations they could make, Myers said. As the researchers continue their work, they may find an even better candidate for eventual drug development.

Yet even at this stage, cresomycin represents an exciting possibility, according to experts who weren’t involved in the work.

“Probably about one in 1,000 projects make it to the level where he’s got it,” said Richard Alm, chief scientific officer at the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator, or CARB-X, which gave Myers the $1.2-million grant. Of potential drugs that make it to the stage of development that cresomycin has reached, Alm estimated that one in every 30 or 40 ultimately has enough positive data to win approval from the U.S. Food and Drug Administration.

CARB-X is a global nonprofit dedicated to speeding up development of new antibiotics. It has made nearly 100 grants so far to companies or academic institutions working to treat, prevent or diagnose antibiotic-resistant infections. Headquartered at Boston University, the accelerator is funded by the governments of the U.S., the United Kingdom, Canada and Germany, as well as the Bill and Melinda Gates Foundation and the Novo Nordisk Foundation.

Development of antibiotics has stalled in part because they aren’t as potentially lucrative as other drugs, Alm said. They aren’t meant to be taken over the long term like medications for chronic conditions like diabetes or high blood pressure. And doctors want to use the most potent ones as rarely as possible, to give bacteria fewer chances to develop resistance to them.

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All of that makes it a lot harder to recoup the costs of producing an effective antibiotic, Alm said. Efforts like CARB-X are an attempt to keep the pipeline from drying up.

“If your house is burning, you don’t have time to buy a fire truck, hire firemen and train them to come and put your fire out. You need them ready to go,” Alm said. “That’s the same with antibiotics. If you go into hospital and you get a superbug, you need an antibiotic that is there on the shelf.”

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Can fire-resistant homes be sexy? ‘You be the judge,’ says this Palisades architect

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Can fire-resistant homes be sexy? ‘You be the judge,’ says this Palisades architect

At first glance, it looks like nothing more than a charming Spanish-revival, quintessentially Californian home — but this Pacific Palisades rebuild is constructed like a tank.

Every exterior wall of the steel-framed home is a foot-thick, fire-resistant barricade. The home is connected to a satellite fire monitoring service. Should a fire start in town, sturdy metal shutters descend to cover every window. An exterior sprinkler system can pump 40,000 gallons of water from giant tanks hidden behind the shrubs in the property’s yard. If the cameras and heat sensors around the house detect danger, the system can envelop the home in over 1,000 gallons of fire retardant and hundreds of gallons of fire-suppressing foam.

Palisades resident and architect Ardie Tavangarian is so confident in his design that he even asked the fire department if they could start a controlled fire on the property to test it all out. (They said no.)

Tavangarian built a career designing multimillion-dollar luxury homes in Los Angeles, but after the Palisades fire destroyed 13 of his works — including his family’s home — he found another calling: how to design a house that can handle what the Santa Monica Mountains throw at it. And how to do it quickly and affordably.

Water tanks form part of a backup water supply in a newly built fire-resistant home in Pacific Palisades.

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“Nature is so powerful,” he said, sitting on a couch in the new house, which he built for his adult twin daughters. “We are guests living in that environment and expecting, ‘Oh, nature is going to be really kind to me.’ No, it’s not. It does what it’s supposed to do.”

Tavangarian watched the Jan. 1 Lachman fire from his property not far from here; a week later that fire rekindled, grew into the Palisades fire, and burned through his house. But the painful details of the fire — the missteps of the fire department, the empty reservoir — didn’t matter when it came to deciding how to rebuild, he said. The reality is, many fires have burned in these mountains. Many more will.

A sprinkler on a roof.

A sprinkler on the roof is part of a house-wide sprinkler system.

For the architect, who has spent much of his 45-year career designing for luxury, hardening a home against wildfire has brought a new kind of luxury to his homes: peace of mind.

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It’s a sentiment that resonates with fire survivors: Tavangarian says he’s received considerable interest from other property owners in the Palisades looking to rebuild their houses.

The metal shutters and advanced outdoor sprinkler system are the flashiest parts of Tavangarian’s home hardening project, and the efficacy of these adaptations is still up for debate. Because the measures have not yet been widely adopted, there are few studies exploring how much or little they protect homes in real-world fires.

Ardie Tavangarian stands inside a house.

Architect Ardie Tavangarian inside the house he designed.

Anecdotal evidence has indicated the effectiveness of sprinklers can vary significantly based on the setup and the conditions during the fire. Extreme wind, for example, can make them less effective. Lab studies have generally found shutters can reduce the risk of windows shattering.

These measures aren’t cheap, either. Sprinkler systems can cost north of $100,000, for example. However, Tavangarian said when all was said and done, the home he built for his daughters cost around $700 per square foot — less than what Palisades residents said they expected to pay, but more than what Altadena residents expected for their rebuilds.

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Tavangarian also hopes to see insurers increasingly consider the home-hardening measures property owners take when writing policies, which he said could potentially offset the extra cost in a decade or less. As he explored getting insurance for the new home, one insurer quoted him $80,000 a year. After he convinced the company to visit the property, it lowered the quote to just $13,000, he said.

A living room inside a fire-resistant house, with metal heat shields drawn over the windows.

The house includes metal heat shields that can drop down if a fire approaches.

The home also has essentially all of the other less flashy — but much cheaper and well-proven — home hardening measures recommended by fire professionals: The underside of the roof’s overhang is closed off — a common place embers enter a home. The roof, where burning embers can accumulate, is made of fire-resistant material. The windows, vulnerable to shattering in extreme heat, are made of a toughened glass. There is virtually no vegetation within the first five feet of the home.

When asked if he felt he had compromised on design, comfort or aesthetics for the extra protection — one of the many concerns Californians have with the state’s draft “Zone Zero” requirements that may significantly limit vegetation within five feet of a home — Tavangarian simply said, “You be the judge.”

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Commentary: My toothache led to a painful discovery: The dental care system is full of cavities as you age

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Commentary: My toothache led to a painful discovery: The dental care system is full of cavities as you age

I had a nagging toothache recently, and it led to an even more painful revelation.

If you X-rayed the state of oral health care in the United States, particularly for people 65 and older, the picture would be full of cavities.

“It’s probably worse than you can even imagine,” said Elizabeth Mertz, a UC San Francisco professor and Healthforce Center researcher who studies barriers to dental care for seniors.

Mertz once referred to the snaggletoothed, gap-filled oral health care system — which isn’t really a system at all — as “a mess.”

But let me get back to my toothache, while I reach for some painkiller. It had been bothering me for a couple of weeks, so I went to see my dentist, hoping for the best and preparing for the worst, having had two extractions in less than two years.

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Let’s make it a trifecta.

My dentist said a molar needed to be yanked because of a cellular breakdown called resorption, and a periodontist in his office recommended a bone graft and probably an implant. The whole process would take several months and cost roughly the price of a swell vacation.

I’m lucky to have a great dentist and dental coverage through my employer, but as anyone with a private plan knows, dental insurance can barely be called insurance. It’s fine for cleanings and basic preventive routines. But for more complicated and expensive procedures — which multiply as you age — you can be on the hook for half the cost, if you’re covered at all, with annual payout caps in the $1,500 range.

“The No. 1 reason for delayed dental care,” said Mertz, “is out-of-pocket costs.”

So I wondered if cost-wise, it would be better to dump my medical and dental coverage and switch to a Medicare plan that costs extra — Medicare Advantage — but includes dental care options. Almost in unison, my two dentists advised against that because Medicare supplemental plans can be so limited.

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Sorting it all out can be confusing and time-consuming, and nobody warns you in advance that aging itself is a job, the benefits are lousy, and the specialty care you’ll need most — dental, vision, hearing and long-term care — are not covered in the basic package. It’s as if Medicare was designed by pranksters, and we’re paying the price now as the percentage of the 65-and-up population explodes.

So what are people supposed to do as they get older and their teeth get looser?

A retired friend told me that she and her husband don’t have dental insurance because it costs too much and covers too little, and it turns out they’re not alone. By some estimates, half of U.S. residents 65 and older have no dental insurance.

That’s actually not a bad option, said Mertz, given the cost of insurance premiums and co-pays, along with the caps. And even if you’ve got insurance, a lot of dentists don’t accept it because the reimbursements have stagnated as their costs have spiked.

But without insurance, a lot of people simply don’t go to the dentist until they have to, and that can be dangerous.

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“Dental problems are very clearly associated with diabetes,” as well as heart problems and other health issues, said Paul Glassman, associate dean of the California Northstate University dentistry school.

There is one other option, and Mertz referred to it as dental tourism, saying that Mexico and Costa Rica are popular destinations for U.S. residents.

“You can get a week’s vacation and dental work and still come out ahead of what you’d be paying in the U.S.,” she said.

Tijuana dentist Dr. Oscar Ceballos told me that roughly 80% of his patients are from north of the border, and come from as far away as Florida, Wisconsin and Alaska. He has patients in their 80s and 90s who have been returning for years because in the U.S. their insurance was expensive, the coverage was limited and out-of-pocket expenses were unaffordable.

“For example, a dental implant in California is around $3,000-$5,000,” Ceballos said. At his office, depending on the specifics, the same service “is like $1,500 to $2,500.” The cost is lower because personnel, office rent and other overhead costs are cheaper than in the U.S., Ceballos said.

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As we spoke by phone, Ceballos peeked into his waiting room and said three patients were from the U.S. He handed his cellphone to one of them, San Diegan John Lane, who said he’s been going south of the border for nine years.

“The primary reason is the quality of the care,” said Lane, who told me he refers to himself as 39, “with almost 40 years of additional” time on the clock.

Ceballos is “conscientious and he has facilities that are as clean and sterile and as medically up to date as anything you’d find in the U.S.,” said Lane, who had driven his wife down from San Diego for a new crown.

“The cost is 50% less than what it would be in the U.S.,” said Lane, and sometimes the savings is even greater than that.

Come this summer, Lane may be seeing even more Californians in Ceballos’ waiting room.

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“Proposed funding cuts to the Medi-Cal Dental program would have devastating impacts on our state’s most vulnerable residents,” said dentist Robert Hanlon, president of the California Dental Assn.

Dental student Somkene Okwuego smiles after completing her work on patient Jimmy Stewart, 83, who receives affordable dental work at the Ostrow School of Dentistry of USC on the USC campus in Los Angeles on February 26, 2026.

(Genaro Molina / Los Angeles Times)

Under Proposition 56’s tobacco tax in 2016, supplemental reimbursements to dentists have been in place, but those increases could be wiped out under a budget-cutting proposal. Only about 40% of the state’s dentists accept Medi-Cal payments as it is, and Hanlon told me a CDA survey indicates that half would stop accepting Medi-Cal patients and many others will accept fewer patients.

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“It’s appalling that when the cost of providing healthcare is at an all-time high, the state is considering cutting program funding back to 1990s levels,” Hanlon said. “These cuts … will force patients to forgo or delay basic dental care, driving completely preventable emergencies into already overcrowded emergency departments.”

Somkene Okwuego, who as a child in South L.A. was occasionally a patient at USC’s Herman Ostrow School of Dentistry clinic, will graduate from the school in just a few months.

I first wrote about Okwuego three years ago, after she got an undergrad degree in gerontology, and she told me a few days ago that many of her dental patients are elderly and have Medi-Cal or no insurance at all. She has also worked at a Skid Row dental clinic, and plans after graduation to work at a clinic where dental care is free or discounted.

Okwuego said “fixing the smiles” of her patients is a privilege and boosts their self-image, which can help “when they’re trying to get jobs.” When I dropped by to see her Thursday, she was with 83-year-old patient Jimmy Stewart.

Stewart, an Army veteran, told me he had trouble getting dental care at the VA and had gone years without seeing a dentist before a friend recommended the Ostrow clinic. He said he’s had extractions and top-quality restorative care at USC, with the work covered by his Medi-Cal insurance.

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I told Stewart there could be some Medi-Cal cuts in the works this summer.

“I’d be screwed,” he said.

Him and a lot of other people.

steve.lopez@latimes.com

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Diablo Canyon clears last California permit hurdle to keep running

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Diablo Canyon clears last California permit hurdle to keep running

Central Coast Water authorities approved waste discharge permits for Diablo Canyon nuclear plant Thursday, making it nearly certain it will remain running through 2030, and potentially through 2045.

The Pacific Gas & Electric-owned plant was originally supposed to shut down in 2025, but lawmakers extended that deadline by five years in 2022, fearing power shortages if a plant that provides about 9 percent the state’s electricity were to shut off.

In December, Diablo Canyon received a key permit from the California Coastal Commission through an agreement that involved PG&E giving up about 12,000 acres of nearby land for conservation in exchange for the loss of marine life caused by the plant’s operations.

Today’s 6-0 vote by the Central Coast Regional Water Board approved PG&E’s plans to limit discharges of pollutants into the water and continue to run its “once-through cooling system.” The cooling technology flushes ocean water through the plant to absorb heat and discharges it, killing what the Coastal Commission estimated to be two billion fish each year.

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The board also granted the plant a certification under the Clean Water Act, the last state regulatory hurdle the facility needed to clear before the federal Nuclear Regulatory Commission (NRC) is allowed to renew its permit through 2045.

The new regional water board permit made several changes since the last one was issued in 1990. One was a first-time limit on the chemical tributyltin-10, a toxic, internationally-banned compound added to paint to prevent organisms from growing on ship hulls.

Additional changes stemmed from a 2025 Supreme Court ruling that said if pollutant permits like this one impose specific water quality requirements, they must also specify how to meet them.

The plant’s biggest water quality impact is the heated water it discharges into the ocean, and that part of the permit remains unchanged. Radioactive waste from the plant is regulated not by the state but by the NRC.

California state law only allows the plant to remain open to 2030, but some lawmakers and regulators have already expressed interest in another extension given growing electricity demand and the plant’s role in providing carbon-free power to the grid.

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Some board members raised concerns about granting a certification that would allow the NRC to reauthorize the plant’s permits through 2045.

“There’s every reason to think the California entities responsible for making the decision about continuing operation, namely the California [Independent System Operator] and the Energy Commission, all of them are sort of leaning toward continuing to operate this facility,” said boardmember Dominic Roques. “I’d like us to be consistent with state law at least, and imply that we are consistent with ending operation at five years.”

Other board members noted that regulators could revisit the permits in five years or sooner if state and federal laws changes, and the board ultimately approved the permit.

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