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Drug can amplify naloxone's effect and reduce opioid withdrawals, study shows

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Drug can amplify naloxone's effect and reduce opioid withdrawals, study shows

Naloxone has long been hailed as a life-saving drug in the face of the opioid epidemic. But its capacity to save someone from an overdose can be limited by the potency of the opioid — a person revived by naloxone can still overdose once it wears off.

Stanford researchers have found a companion drug that can enhance naloxone’s effect — and reduce withdrawal symptoms. Their research on mice, led by Stanford University postdoctoral scholar Evan O’Brien, was published today in Nature.

Typically, overdose deaths occur when opioids bind to the part of the brain that controls breathing, slowing it to a stop. Naloxone reverses overdoses by kicking opioids off pain receptors and allowing normal breathing to resume.

However, it is only able to occupy pain receptors for 30 to 90 minutes. For more potent opioids, such as fentanyl, that may not be long enough.

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To determine how the naloxone companion drug, which researchers are calling compound 368, might boost naloxone’s effectiveness, researchers conducted an experiment on pain tolerance in mice, said Jay McLaughlin, a professor of pharmacology at the University of Florida. How quickly would mice pull their tails out of hot water, depending on which combination of opioids and treatments they were given?

Mice that were injected with only morphine did not respond to the hot water — given their dulled pain receptors. Mice given morphine and naloxone pulled their tails out within seconds. No surprises yet.

When the dosage of naloxone was reduced and compound 368 was added, the compound was found to amplify naloxone’s effects, as if a regular dose was used. When used on its own, the compound had no effect, indicating that it is only helpful in increasing the potency of naloxone.

What researchers did not expect, however, was that the compound reduced withdrawal symptoms.

McLaughlin said withdrawal is one reason that people who have become physically dependent on opioids may avoid naloxone.

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“Opioid withdrawal will not kill you, but I have talked to a number of people who have gone through it, and they have all said the same thing: … ‘I wished I was dead,’” McLaughlin said. “It has a massive range of nasty, horrible effects.”

The idea that the compound could amplify naloxone’s effect at a lower dosage, while limiting withdrawal symptoms, indicates that it may be a “new therapeutic approach” to overdose response, McLaughlin said.

The research team said their next step is to tweak the compound and dosage so that the effects of naloxone last long enough to reverse overdoses of more potent drugs.

Though the compound is not yet ready for human trials, the researchers chose to release their findings in the hope that their peers can double check and improve upon their work, said Susruta Majumdar, another senior author and a professor of anesthesiology at the Washington University School of Medicine in St. Louis.

“We may not be able to get that drug into the clinic, but somebody else may,” Majumdar said. He added: “Let them win the race.”

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Notorious ‘winter vomiting bug’ rising in California. A new norovirus strain could make it worse

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Notorious ‘winter vomiting bug’ rising in California. A new norovirus strain could make it worse

The dreaded norovirus — the “vomiting bug” that often causes stomach flu symptoms — is climbing again in California, and doctors warn that a new subvariant could make even more people sick this season.

In L.A. County, concentrations of norovirus are already on the rise in wastewater, indicating increased circulation of the disease, the local Department of Public Health told the Los Angeles Times.

Norovirus levels are increasing across California, and the rise is especially notable in the San Francisco Bay Area and L.A., according to the California Department of Public Health.

And the rate at which norovirus tests are confirming infection is rising nationally and in the Western U.S. For the week that ended Nov. 22, the test positivity rate nationally was 11.69%, up from 8.66% two months earlier. In the West, it was even worse: 14.08%, up from 9.59%, according to the U.S. Centers for Disease Control and Prevention.

Norovirus is extraordinarily contagious, and is America’s leading cause of vomiting and diarrhea, according to the CDC. Outbreaks typically happen in the cooler months between November and April.

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Clouding the picture is the recent emergence of a new norovirus strain — GII.17. Such a development can result in 50% more norovirus illness than typical, the CDC says.

“If your immune system isn’t used to something that comes around, a lot of people get infected,” said Dr. Peter Chin-Hong, an infectious diseases expert at UC San Francisco.

During the 2024-25 winter season, GII.17 overthrew the previous dominant norovirus strain, GII.4, that had been responsible for more than half of national norovirus outbreaks over the preceding decade. The ancestor of the GII.17 strain probably came from a subvariant that triggered an outbreak in Romania in 2021, according to CDC scientists.

GII.17 vaulted in prominence during last winter’s norovirus surge and was ultimately responsible for about 75% of outbreaks of the disease nationally.

The strain’s emergence coincided with a particularly bad year for norovirus, one that started unusually early in October 2024, peaked earlier than normal the following January and stretched into the summer, according to CDC scientists writing in the journal Emerging Infectious Diseases.

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During the three prior seasons, when GII.4 was dominant, norovirus activity had been relatively stable, Chin-Hong said.

Norovirus can cause substantial disruptions — as many parents know all too well. An elementary school in Massachusetts was forced to cancel all classes on Thursday and Friday because of the “high volume of stomach illness cases,” which was suspected to be driven by norovirus.

More than 130 students at Roberts Elementary School in Medford, Mass., were absent Wednesday, and administrators said there probably wouldn’t be a “reasonable number of students and staff” to resume classes Friday. A company was hired to perform a deep clean of the school’s classrooms, doorknobs and kitchen equipment.

Some places in California, however, aren’t seeing major norovirus activity so far this season. Statewide, while norovirus levels in wastewater are increasing, they still remain low, the California Department of Public Health said.

There have been 32 lab-confirmed norovirus outbreaks reported to the California Department of Public Health so far this year. Last year, there were 69.

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Officials caution the numbers don’t necessarily reflect how bad norovirus is in a particular year, as many outbreaks are not lab-confirmed, and an outbreak can affect either a small or large number of people.

Between Aug. 1 and Nov. 13, there were 153 norovirus outbreaks publicly reported nationally, according to the CDC. During the same period last year, there were 235.

UCLA hasn’t reported an increase in the number of norovirus tests ordered, nor has it seen a significant increase in test positivity rates. Chin-Hong said he likewise hasn’t seen a big increase at UC San Francisco.

“Things are relatively still stable clinically in California, but I think it’s just some amount of time before it comes here,” Chin-Hong said.

In a typical year, norovirus causes 2.27 million outpatient clinic visits, mostly young children; 465,000 emergency department visits, 109,000 hospitalizations, and 900 deaths, mostly among seniors age 65 and older.

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People with severe ongoing vomiting, profound diarrhea and dehydration may need to seek medical attention to get hydration intravenously.

“Children who are dehydrated may cry with few or no tears and be unusually sleepy or fussy,” the CDC says. Sports drinks can help with mild dehydration, but what may be more helpful are oral rehydration fluids that can be bought over the counter.

Children under the age of 5 and adults 85 and older are most likely to need to visit an emergency room or clinic because of norovirus, and should not hesitate to seek care, experts say.

“Everyone’s at risk, but the people who you worry about, the ones that we see in the hospital, are the very young and very old,” Chin-Hong said.

Those at highest risk are babies, because it doesn’t take much to cause potentially serious problems. Newborns are at risk for necrotizing enterocolitis, a life-threatening inflammation of the intestine that virtually only affects new babies, according to the National Library of Medicine.

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Whereas healthy people generally clear the virus in one to three days, immune-compromised individuals can continue to have diarrhea for a long time “because their body’s immune system can’t neutralize the virus as effectively,” Chin-Hong said.

The main way people get norovirus is by accidentally drinking water or eating food contaminated with fecal matter, or touching a contaminated surface and then placing their fingers in their mouths.

People usually develop symptoms 12 to 48 hours after they’re exposed to the virus.

Hand sanitizer does not work well against norovirus — meaning that proper handwashing is vital, experts say.

People should lather their hands with soap and scrub for at least 20 seconds, including the back of their hands, between their fingers and under their nails, before rinsing and drying, the CDC says.

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One helpful way to keep track of time is to hum the “Happy Birthday” song from beginning to end twice, the CDC says. Chin-Hong says his favorite is the chorus of Kelly Clarkson’s “Since U Been Gone.”

If you’re living with someone with norovirus, “you really have to clean surfaces and stuff if they’re touching it,” Chin-Hong said. Contamination is shockingly easy. Even just breathing out little saliva droplets on food that is later consumed by someone else can spread infection.

Throw out food that might be contaminated with norovirus, the CDC says. Noroviruses are relatively resistant to heat and can survive temperatures as high as 145 degrees.

Norovirus is so contagious that even just 10 viral particles are enough to cause infection. By contrast, it takes ingesting thousands of salmonella particles to get sick from that bacterium.

People are most contagious when they are sick with norovirus — but they can still be infectious even after they feel better, the CDC says.

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The CDC advises staying home for 48 hours after infection. Some studies have even shown that “you can still spread norovirus for two weeks or more after you feel better,” according to the CDC.

The CDC also recommends washing laundry in hot water.

Besides schools, other places where norovirus can spread quickly are cruise ships, day-care centers and prisons, Chin-Hong said.

The most recent norovirus outbreak on a cruise ship reported by the CDC is on the ship AIDAdiva, which set sail on Nov. 10 from Germany. Out of 2,007 passengers on board, 4.8% have reported being ill. The outbreak was first reported on Nov. 30 following stops that month at the Isle of Portland, England; Halifax, Canada; Boston; New York City; Charleston, S.C.; and Miami.

According to CruiseMapper, the ship was set to make stops in Puerto Vallarta on Saturday, San Diego on Tuesday, Los Angeles on Wednesday, Santa Barbara on Thursday and San Francisco between Dec. 19-21.

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Southern California mountain lions recommended for threatened status

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Southern California mountain lions recommended for threatened status

The California Department of Fish and Wildlife has recommended granting threatened species status to roughly 1,400 mountain lions roaming the Central Coast and Southern California, pointing to grave threats posed by freeways, rat poison and fierce wildfires.

The determination, released Wednesday, is not the final say but signals a possibility that several clans of the iconic cougars will be listed under the California Endangered Species Act.

It’s a move that supporters say would give the vulnerable animals a chance at recovery, but detractors have argued would make it harder to get rid of lions that pose a safety risk to people and livestock.

The recommendation was “overdue,” Charlton Bonham, director of the state wildlife department, said during a California Fish and Game Commission meeting.

It arrives about six years after the Center for Biological Diversity and Mountain Lion Foundation petitioned the commission to consider listing a half-dozen isolated lion populations that have suffered from being hit by cars, poisoned by rodenticides and trapped by development.

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The following year, in 2020 the Commission found the request might be warranted, giving the lions temporary endangered species protections as “candidates” for listing. It also prompted the state wildlife department to put together a report to inform the commission’s final decision.

The next step is for state wildlife commissioners to to vote on the protections, possibly in February.

Brendan Cummings, conservation director for Center for Biological Diversity, hailed the moment as “a good day, not just for mountain lions, but for Californians.”

If the commissioners adopt the recommendation, as he believes they will, then the “final listing of the species removes any uncertainty about the state’s commitment to conserving and recovering these ecologically important, charismatic and well-loved species that are so much a part of California.”

The report recommends listing lions “in an area largely coinciding” with what the petitioners requested, which includes the Santa Ana, San Gabriel, San Bernardino, Santa Monica, Santa Cruz and Tehachapi mountains.

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It trims off portions along the northern and eastern borders of what was proposed, including agricultural lands in the Bay Area and a southeastern portion of desert — areas where state experts had no records of lions, according to Cummings.

Officials in the report note that most of the lion groups proposed for listing are contending with a lack of gene flow because urban barriers keep them from reaching one another.

In Southern California, lions have shown deformities from inbreeding, including kinked tails and malformed sperm. There’s an almost 1 in 4 chance, according to research, that mountain lions could become extinct in the Santa Monica and Santa Ana mountains within 50 years.

The late P-22 — a celebrity mountain lion that inhabited Griffith Park – personified the tribulations facing his kind. Rat poison and car collisions battered him from the inside out. He was captured and euthanized in late 2022, deemed too sick to return to the wild because of injuries and infection.

For some species, protections come in the form of stopping chainsaws or bulldozers. But imperiled lions, Cummings said, need their habitats stitched together in the form of wildlife crossings — such as the gargantuan one being built over the 101 Freeway in Agoura Hills. He added that developments that could restrict their movement should get more scrutiny under the proposed protections.

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Critics of the effort to list lion populations have said that it will stymie residential and commercial projects.

California is home to roughly 4,170 mountain lions, according to the recent report, but not all are equal in their struggle.

Many lion populations, particularly in northwest coastal forests, are hearty and healthy.

Protections are not being sought for those cats. Some, in fact, would like to see their numbers reduced amid some high-profile conflicts.

Bonham, the director of the state Department of Fish and Wildlife, spoke to concerns about public safety at the recent meeting, alluding to the tragic death of young man who was mauled by a cougar last year in Northern California.

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“These are really delicate issues and the conversation I know in the coming years is going to have to grapple with all that,” said Bonham, who will be stepping down this month after nearly 15 years in his role.

California’s lions already enjoy certain protections. In 1990, voters approved a measure that designated them a “specially protected species” and banned hunting them for sport.

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California’s last nuclear plant clears major hurdle to power on

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California’s last nuclear plant clears major hurdle to power on

California environmental regulators on Thursday struck a landmark deal with Pacific Gas & Electric to extend the life of the state’s last remaining nuclear power plant in exchange for thousands of acres of new land conservation in San Luis Obispo County.

PG&E’s agreement with the California Coastal Commission is a key hurdle for the Diablo Canyon nuclear plant to remain online until at least 2030. The plant was slated to close this year, largely due to concerns over seismic safety, but state officials pushed to delay it — saying the plant remains essential for the reliable operation of California’s electrical grid. Diablo Canyon provides nearly 9% of the electricity generated in the state, making it the state’s single largest source.

The Coastal Commission voted 9-3 to approve the plan, settling the fate of some 12,000 acres that surround the power plant as a means of compensation for environmental harm caused by its continued operation.

Nuclear power does not emit greenhouse gases. But Diablo Canyon uses an estimated 2.5 billion gallons of ocean water each day to absorb heat in a process known as “once-through cooling,” which kills an estimated two billion or more marine organisms each year.

Some stakeholders in the region celebrated the conservation deal, while others were disappointed by the decision to trade land for marine impacts — including a Native tribe that had hoped the land would be returned to them. Diablo Canyon sits along one of the most rugged and ecologically rich stretches of the California coast.

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Under the agreement, PG&E will immediately transfer a 4,500-acre parcel on the north side of the property known as the “North Ranch” into a conservation easement and pursue transfer of its ownership to a public agency such as the California Department of Parks and Recreation, a nonprofit land conservation organization or tribe. A purchase by State Parks would result in a more than 50% expansion of the existing Montaña de Oro State Park.

PG&E will also offer a 2,200-acre parcel on the southern part of the property known as “Wild Cherry Canyon” for purchase by a government agency, nonprofit land conservation organization or tribe. In addition, the utility will provide $10 million to plan and manage roughly 25 miles of new public access trails across the entire property.

“It’s going to be something that changes lives on the Central Coast in perpetuity,” Commissioner Christopher Lopez said at the meeting. “This matters to generations that have yet to exist on this planet … this is going to be a place that so many people mark in their minds as a place that transforms their lives as they visit and recreate and love it in a way most of us can’t even imagine today.”

Critically, the plan could see Diablo Canyon remain operational much longer than the five years dictated by Thursday’s agreement. While the state Legislature only authorized the plant to operate through 2030, PG&E’s federal license renewal would cover 20 years of operations, potentially keeping it online until 2045.

Should that happen, the utility would need to make additional land concessions, including expanding an existing conservation area on the southern part of the property known as the “South Ranch” to 2,500 acres. The plan also includes rights of first refusal for a government agency or a land conservation group to purchase the entirety of the South Ranch, 5,000 acres, along with Wild Cherry Canyon — after 2030.

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Pelicans along the concrete breakwater at Pacific Gas and Electric's Diablo Canyon Power Plant

Pelicans along the concrete breakwater at Pacific Gas and Electric’s Diablo Canyon Power Plant

(Brian van der Brug/Los Angeles Times)

Many stakeholders were frustrated by the carve-out for the South Ranch, but still saw the agreement as an overall victory for Californians.

“It is a once in a lifetime opportunity,” Sen. John Laird (D-Santa Cruz) said in a phone call ahead of Thursday’s vote. “I have not been out there where it has not been breathtakingly beautiful, where it is not this incredible, unique location, where you’re not seeing, for much of it, a human structure anywhere. It is just one of those last unique opportunities to protect very special land near the California coast.”

Others, however, described the deal as disappointing and inadequate.

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That includes many of the region’s Native Americans who said they felt sidelined by the agreement. The deal does not preclude tribal groups from purchasing the land in the future, but it doesn’t guarantee that or give them priority.

The yak titʸu titʸu yak tiłhini Northern Chumash Tribe of San Luis Obispo County and Region, which met with the Coastal Commission several times in the lead-up to Thursday’s vote, had hoped to see the land returned to them.

Scott Lanthrop is a member of the tribe’s board and has worked on the issue for several years.

“The sad part is our group is not being recognized as the ultimate conservationist,” he told The Times. “Any normal person, if you ask the question, would you rather have a tribal group that is totally connected to earth and wind and water, or would you like to have some state agency or gigantic NGO manage this land, I think the answer would be, ‘Hey, you probably should give it back to the tribe.’”

Tribe chair Mona Tucker said she fears that free public access to the land could end up harming it instead of helping it, as the Coastal Commission intends.

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“In my mind, I’m not understanding how taking the land … is mitigation for marine life,” Tucker said. “It doesn’t change anything as far as impacts to the water. It changes a lot as far as impacts to the land.”

Montaña de Oro State Park.

Montaña de Oro State Park.

(Christopher Reynolds / Los Angeles Times)

The deal has been complicated by jurisdictional questions, including who can determine what happens to the land. While PG&E owns the North Ranch parcel that could be transferred to State Parks, the South Ranch and Wild Cherry Canyon are owned by its subsidiary, Eureka Energy Company.

What’s more, the California Public Utilities Commission, which regulates utilities such as PG&E, has a Tribal Land Transfer Policy that calls for investor-owned power companies to transfer land they no longer want to Native American tribes.

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In the case of Diablo Canyon, the Coastal Commission became the decision maker because it has the job of compensating for environmental harm from the facility’s continued operation. Since the commission determined Diablo’s use of ocean water can’t be avoided, it looked at land conservation as the next best method.

This “out-of-kind” trade-off is a rare, but not unheard of way of making up for the loss of marine life. It’s an approach that is “feasible and more likely to succeed” than several other methods considered, according to the commission’s staff report.

“This plan supports the continued operation of a major source of reliable electricity for California, and is in alignment with our state’s clean energy goals and focus on coastal protection,” Paula Gerfen, Diablo Canyon’s senior vice president and chief nuclear officer, said in a statement.

But Assemblymember Dawn Addis (D-Morro Bay) said the deal was “not the best we can do” — particularly because the fate of the South Ranch now depends on the plant staying in operation beyond 2030.

“I believe the time really is now for the immediate full conservation of the 12,000 [acres], and to bring accountability and trust back for the voters of San Luis Obispo County,” Addis said during the meeting.

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There are also concerns about the safety of continuing to operate a nuclear plant in California, with its radioactive waste stored in concrete casks on the site. Diablo Canyon is subject to ground shaking and earthquake hazards, including from the nearby Hosgri Fault and the Shorline Fault, about 2.5 miles and 1 mile from the facility, respectively.

PG&E says the plant has been built to withstand hazards. It completed a seismic hazard assessment in 2024, and determined Diablo Canyon is safe to continue operation through 2030. The Coastal Commission, however, found if the plant operates longer, it would warrant further seismic study.

A key development for continuing Diablo Canyon’s operation came in 2022 with Senate Bill 846, which delayed closure by up to five additional years. At the time, California was plagued by rolling blackouts driven extreme heat waves, and state officials were growing wary about taking such a major source of power offline.

But California has made great gains in the last several years — including massive investments in solar energy and battery storage — and some questioned whether the facility is still needed at all.

Others said conserving thousands of acres of land still won’t make up for the harms to the ocean.

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“It is unmitigatable,” said David Weisman, executive director of the nonprofit Alliance for Nuclear Responsibility. He noted that the Coastal Commission’s staff report says it would take about 99 years to balance the loss of marine life with the benefits provided by 4,500 acres of land conservation. Twenty more years of operation would take about 305 years to strike that same balance.

But some pointed out that neither the commission nor fisheries data find Diablo’s operations cause declines in marine life. Ocean harm may be overestimated, said Seaver Wang, an oceanographer and the climate and energy director at the Breakthrough Institute, a Berkeley-based research center.

In California’s push to transition to clean energy, every option comes with downsides, Wang said. In the case of nuclear power — which produces no greenhouse gas emissions — it’s all part of the trade off, he said.

“There’s no such thing as impacts-free energy,” he said.

The Coastal Commission’s vote is one of the last remaining obstacles to keeping the plant online. PG&E will also need a final nod from the Regional Water Quality Control Board, which decides on a pollution discharge permit in February.

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The federal Nuclear Regulatory Commission will also have to sign off on Diablo’s extension.

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