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What Nearly Brainless Rodents Know About Weight Loss and Hunger

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What Nearly Brainless Rodents Know About Weight Loss and Hunger

Do we really have free will when it comes to eating? It’s a vexing question that is at the heart of why so many people find it so difficult to stick to a diet.

To get answers, one neuroscientist, Harvey J. Grill of the University of Pennsylvania, turned to rats and asked what would happen if he removed all of their brains except their brainstems. The brainstem controls basic functions like heart rate and breathing. But the animals could not smell, could not see, could not remember.

Would they know when they had consumed enough calories?

To find out, Dr. Grill dripped liquid food into their mouths.

“When they reached a stopping point, they allowed the food to drain out of their mouths,” he said.

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Those studies, initiated decades ago, were a starting point for a body of research that has continually surprised scientists and driven home that how full animals feel has nothing to do with consciousness. The work has gained more relevance as scientists puzzle out how exactly the new drugs that cause weight loss, commonly called GLP-1s and including Ozempic, affect the brain’s eating-control systems.

The story that is emerging does not explain why some people get obese and others do not. Instead, it offers clues about what makes us start eating, and when we stop.

While most of the studies were in rodents, it defies belief to think that humans are somehow different, said Dr. Jeffrey Friedman, an obesity researcher at Rockefeller University in New York. Humans, he said, are subject to billions of years of evolution leading to elaborate neural pathways that control when to eat and when to stop eating.

As they have probed how eating is controlled, researchers learned that the brain is steadily getting signals that hint at how calorically dense a food is. There’s a certain amount of calories that the body needs, and these signals make sure the body gets them.

The process begins before a lab animal takes a single bite. Just the sight of food spurs neurons to anticipate whether a lot of calories will be packed into that food. The neurons respond more strongly to a food like peanut butter — loaded with calories — than to a low-calorie one like mouse chow.

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The next control point occurs when the animal tastes the food: Neurons calculate the caloric density again from signals sent from the mouth to the brainstem.

Finally, when the food makes its way to the gut, a new set of signals to the brain lets the neurons again ascertain the caloric content.

And it is actually the calorie content that the gut assesses, as Zachary Knight, a neuroscientist at the University of California San Francisco, learned.

He saw this when he directly infused three types of food into the stomachs of mice. One infusion was of fatty food, another of carbohydrates and the third of protein. Each infusion had the same number of calories.

In each case, the message to the brain was the same: The neurons were signaling the amount of energy, in the form of calories, and not the source of the calories.

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When the brain determines enough calories were consumed, neurons send a signal to stop eating.

Dr. Knight said these discoveries surprised him. He’d always thought that the signal to stop eating would be “a communication between the gut and the brain,” he said. There would be a sensation of having a full stomach and a deliberate decision to stop eating.

Using that reasoning, some dieters try to drink a big glass of water before a meal, or fill up on low-calorie foods, like celery.

But those tricks have not worked for most people because they don’t account for how the brain controls eating. In fact, Dr. Knight found that mice do not even send satiety signals to the brain when all they are getting is water.

It is true that people can decide to eat even when they are sated, or can decide not to eat when they are trying to lose weight. And, Dr. Grill said, in an intact brain — not just a brainstem — other areas of the brain also exert control.

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But, Dr. Friedman said, in the end the brain’s controls typically override a person’s conscious decisions about whether they feel a need to eat. He said, by analogy, you can hold your breath — but only for so long. And you can suppress a cough — but only up to a point.

Scott Sternson, a neuroscientist with the University of California in San Diego and Howard Hughes Medical Institute, agreed.

“There is a very large proportion of appetite control that is automatic,” said Dr. Sternson, who is also a co-founder of a startup company, Penguin Bio, that is developing obesity treatments. People can decide to eat or not at a given moment. But, he added, maintaining that sort of control uses a lot of mental resources.

“Eventually, attention goes to other things and the automatic process will wind up dominating,” he said.

As they probed the brain’s eating-control systems, researchers were continually surprised.

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They learned, for example, about the brain’s rapid response to just the sight of food.

Neuroscientists had found in mice a few thousand neurons in the hypothalamus, deep in the brain, that responded to hunger. But how are they regulated? They knew from previous studies that fasting turned these hunger neurons on and that the neurons were less active when an animal was well fed.

Their theory was that the neurons were responding to the body’s fat stores. When fat stores were low — as happens when an animal fasts, for example — levels of leptin, a hormone released from fat, also are low. That would turn the hunger neurons on. As an animal eats, its fat stores are replenished, leptin levels go up, and the neurons, it was assumed, would quiet down.

The whole system was thought to respond only slowly to the state of energy storage in the body.

But then three groups of researchers, independently led by Dr. Knight, Dr. Sternson and Mark Andermann of Beth Israel Deaconess Medical Center, examined the moment-to-moment activity of the hunger neurons.

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They began with hungry mice. Their hunger neurons were firing rapidly, a sign the animals needed food.

The surprise happened when the investigators showed the animals food.

“Even before the first bite of food, the activity of those neurons shut off,” Dr. Knight said. “The neurons were making a prediction. The mouse looks at food. The mouse predicts how many calories it will eat.”

The more calorie-rich the food, the more neurons turn off.

“All three labs were shocked,” said Dr. Bradford B. Lowell, who worked with Dr. Andermann at Beth Israel Deaconess. “It was very unexpected.”

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Dr. Lowell then asked what might happen if he deliberately turned off the hunger neurons even though the mice hadn’t had much to eat. Researchers can do this with genetic manipulations that mark neurons so they can turn them on and off with either a drug or with a blue light.

These mice would not eat for hours, even with food right in front of them.

Dr. Lowell and Dr. Sternson independently did the opposite experiment, turning the neurons on in mice that had just had a huge meal, the mouse equivalent of a Thanksgiving dinner. The animals were reclining, feeling stuffed.

But, said Dr. Andermann, who repeated the experiment, when they turned the hunger neurons on, “The mouse gets up and eats another 10 to 15 percent of its body weight.” He added, “The neurons are saying, ‘Just focus on food.’”

Researchers continue to be amazed by what they are finding — layers of controls in the brain that ensure eating is rigorously regulated. And hints of new ways to develop drugs to control eating.

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One line of evidence was discovered by Amber Alhadeff, a neuroscientist at the Monell Chemical Senses Center and the University of Pennsylvania. She recently found two separate groups of neurons in the brainstem that respond to the GLP-1 obesity drugs.

One group of neurons signaled that the animals have had enough to eat. The other group caused the rodent equivalent of nausea. The current obesity drugs hit both groups of neurons, she reports, which may be a factor in the side effects many feel. She proposes that it might be possible to develop drugs that hit the satiety neurons but not the nausea ones.

Alexander Nectow, of Columbia University, has another surprise discovery. He identified a group of neurons in the brainstem that regulate how big a meal is desired, tracking each bite of food. “We don’t know how they do it,” he said.

“I’ve been studying this brainstem region for a decade and a half,” Dr. Nectow said, “but when we went and used all of our fancy tools, we found this population of neurons we had never studied.”

He’s now asking if the neurons could be targets for a class of weight loss drugs that could upstage the GLP-1s.

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“That would be really amazing,” Dr. Nectow said.

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A virus without a vaccine or treatment is hitting California. What you need to know

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A virus without a vaccine or treatment is hitting California. What you need to know

A respiratory virus that doesn’t have a vaccine or a specific treatment regimen is spreading in some parts of California — but there’s no need to sound the alarm just yet, public health officials say.

A majority of Northern California communities have seen high concentrations of human metapneumovirus, or HMPV, detected in their wastewater, according to data from the WastewaterScan Dashboard, a public database that monitors sewage to track the presence of infectious diseases.

A Los Angeles Times data analysis found the communities of Merced in the San Joaquin Valley, and Novato and Sunnyvale in the San Francisco Bay Area have seen increases in HMPV levels in their wastewater between mid-December and the end of February.

HMPV has also been detected in L.A. County, though at levels considered low to moderate at this point, data show.

While HMPV may not necessarily ring a bell, it isn’t a new virus. Its typical pattern of seasonal spread was upended by the COVID-19 pandemic, and its resurgence could signal a return to a more typical pre-coronavirus respiratory disease landscape.

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Here’s what you need to know.

What is HMPV?

HMPV was first detected in 2001, according to the U.S. Centers for Disease Control and Prevention. It’s transmitted by close contact with someone who is infected or by touching a contaminated surface, said Dr. Neha Nanda, chief of infectious diseases and hospital epidemiologist for Keck Medicine of USC.

Like other respiratory illnesses, such as influenza, HMPV spreads and is more durable in colder temperatures, infectious-disease experts say.

Human metapneumovirus cases commonly start showing up in January before peaking in March or April and then tailing off in June, said Dr. Jessica August, chief of infectious diseases at Kaiser Permanente Santa Rosa.

However, as was the case with many respiratory viruses, COVID disrupted that seasonal trend.

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Why are we talking about HMPV now?

Before the pandemic hit in 2020, Americans were regularly exposed to seasonal viruses like HMPV and developed a degree of natural immunity, August said.

That protection waned during the pandemic, as people stayed home or kept their distance from others. So when people resumed normal activities, they were more vulnerable to the virus. Unlike other viruses, there isn’t a vaccine for human metapneumovirus.

“That’s why after the pandemic we saw record-breaking childhood viral illnesses because we lacked the usual immunity that we had, just from lack of exposure,” August said. “All of that also led to longer viral seasons, more severe illness. But all of these things have settled down in many respects.”

In 2024, the national test positivity for HMPV peaked at 11.7% at the end of March, according to the National Respiratory and Enteric Virus Surveillance System. The following year’s peak was 7.15% in late April.

So far this year, the highest test positivity rate documented was 6.1%, reported on Feb. 21 — the most recent date for which complete data are available.

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While the seasonal spread of viruses like HMPV is nothing new, people became more aware of infectious diseases and how to prevent them during the pandemic, and they’ve remained part of the public consciousness in the years since, August and Nanda said.

What are the symptoms of HMPV?

Most people won’t go to the doctor if they have HMPV because it typically causes mild, cold-like symptoms that include cough, fever, nasal congestion and sore throat.

HMPV infection can progress to:

  • An asthma attack and reactive airway disease (wheezing and difficulty breathing)
  • Middle ear infections behind the ear drum
  • Croup, also known as “barking” cough — an infection of the vocal cords, windpipe and sometimes the larger airways in the lungs
  • Bronchitis
  • Fever

Anyone can contract human metapneumovirus, but those who are immunocompromised or have other underlying medical conditions are at particular risk of developing severe disease — including pneumonia. Young children and older adults are also considered higher-risk groups, Nanda said.

What is the treatment for HMPV?

There is no specified treatment protocol or antiviral medication for HMPV. However, it’s common for an infection to clear up on its own and treatment is mostly geared toward soothing symptoms, according to the American Lung Assn.

A doctor will likely send you home and tell you to rest and drink plenty of fluids, Nanda said.

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If symptoms worsen, experts say you should contact your healthcare provider.

How to avoid contracting HMPV

Infectious-disease experts said the best way to avoid contracting HMPV is similar to preventing other respiratory illnesses.

The American Lung Assn.’s recommendations include:

  • Wash your hands often with soap and water. If that’s not available, clean your hands with an alcohol-based hand sanitizer.
  • Clean frequently touched surfaces.
  • Crack open a window to improve air flow in crowded spaces.
  • Avoid being around sick people if you can.
  • Avoid touching your eyes, nose and mouth.

Assistant data and graphics editor Vanessa Martínez contributed to this report.

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After rash of overdose deaths, L.A. banned sales of kratom. Some say they lost lifeline for pain and opioid withdrawal

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After rash of overdose deaths, L.A. banned sales of kratom. Some say they lost lifeline for pain and opioid withdrawal

Nearly four months ago, Los Angeles County banned the sale of kratom, as well as 7-OH, the synthetic version of the alkaloid that is its active ingredient. The idea was to put an end to what at the time seemed like a rash of overdose deaths related to the drug.

It’s too soon to tell whether kratom-related deaths have dissipated as a result — or, really, whether there was ever actually an epidemic to begin with. But many L.A. residents had become reliant on kratom as something of a panacea for debilitating pain and opioid withdrawal symptoms, and the new rules have made it harder for them to find what they say has been a lifesaving drug.

Robert Wallace started using kratom a few years ago for his knees. For decades he had been in pain, which he says stems from his days as a physical education teacher for the Glendale Unified School District between 1989 and 1998, when he and his students primarily exercised on asphalt.

In 2004, he had arthroscopic surgery on his right knee, followed by varicose vein surgery on both legs. Over the next couple of decades, he saw pain-management specialists regularly. But the primary outcome was a growing dependence on opioid-based painkillers. “I found myself seeking doctors who would prescribe it,” he said.

He leaned on opioids when he could get them and alcohol when he couldn’t, resulting in a strain on his marriage.

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When Wallace was scheduled for his first knee replacement in 2021 (he had his other knee replaced a few years later), his brother recommended he take kratom for the post-surgery pain.

It seemed to work: Wallace said he takes a quarter of a teaspoon of powdered kratom twice a day, and it lets him take charge of managing his pain without prescription painkillers and eases harsh opiate-withdrawal symptoms.

He’s one of many Angelenos frustrated by recent efforts by the county health department to limit access to the drug. “Kratom has impacted my life in only positive ways,” Wallace told The Times.

For now, Wallace is still able to get his kratom powder, called Red Bali, by ordering from a company in Florida.

However, advocates say that the county crackdown on kratom could significantly affect the ability of many Angelenos to access what they say is an affordable, safer alternative to prescription painkillers.

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Kratom comes from the leaves of a tree native to Southeast Asia called Mitragyna speciosa. It has been used for hundreds of years to treat chronic pain, coughing and diarrhea as well as to boost energy — in low doses, kratom appears to act as a stimulant, though in higher doses, it can have effects more like opioids.

Though advocates note that kratom has been used in the U.S. for more than 50 years for all sorts of health applications, there is limited research that suggests kratom could have therapeutic value, and there is no scientific consensus.

Then there’s 7-OH, or 7-Hydroxymitragynine, a synthetic alkaloid derived from kratom that has similar effects and has been on the U.S. market for only about three years. However, because of its ability to bind to opioid receptors in the body, it has a higher potential for abuse than kratom.

Public health officials and advocates are divided on kratom. Some say it should be heavily regulated — and 7-OH banned altogether — while others say both should be accessible, as long as there are age limitations and proper labeling, such as with alcohol or cannabis.

In the U.S., kratom and 7-OH can be found in all sorts of forms, including powder, capsules and liquids — though it depends on exactly where you are in the country. Though the Food and Drug Administration has recommended that 7-OH be included as a Schedule 1 controlled substance under the Controlled Substances Act, that hasn’t been made official. And the plant itself remains unscheduled on the federal level.

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That has left states, counties and cities to decide how to regulate the substances.

California failed to approve an Assembly bill in 2024 that would have required kratom products to be registered with the state, have labeling and warnings, and be prohibited from being sold to anyone younger than 21.

It would also have banned products containing synthetic versions of kratom alkaloids. The state Legislature is now considering another bill that basically does the same without banning 7-OH — while also limiting the amount of synthetic alkaloids in kratom and 7-OH products sold in the state.

“Until kratom and its pharmacologically active key ingredients mitragynine and 7-OH are approved for use, they will remain classified as adulterants in drugs, dietary supplements and foods,” a California Department of Public Health spokesperson previously told The Times.

On Tuesday, California Gov. Gavin Newsom announced that the state’s efforts to crack down on kratom products has resulted in the removal of more than 3,300 kratom and 7-OH products from retail stores. According to a news release from the governor’s office, there has been a 95% compliance rate from businesses in removing the products.

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(Los Angeles Times photo illustration; source photos by Getty Images)

Newsom has equated these actions to the state’s efforts in 2024 to quash the sale of hemp products containing cannabinoids such as THC. Under emergency state regulations two years ago, California banned these specific hemp products and agents with the state Department of Alcoholic Beverage Control seized thousands of products statewide.

Since the beginning of 2026, there have been no reported violations of the ban on sales of such products.

“We’ve shown with illegal hemp products that when the state sets clear expectations and partners with businesses, compliance follows,” Newsom said in a statement. “This effort builds on that model — education first, enforcement where necessary — to protect Californians.”

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Despite the state’s actions, the Los Angeles County Board of Supervisors is still considering whether to regulate kratom, or ban it altogether.

The county Public Health Department’s decision to ban the sale of kratom didn’t come out of nowhere. As Maral Farsi, deputy director of the California Department of Public Health, noted during a Feb. 18 state Senate hearing, the agency “identified 362 kratom-related overdose deaths in California between 2019 and 2023, with a steady increase from 38 in 2019 up to 92 in 2023.”

However, some experts say those numbers aren’t as clear-cut as they seem.

For example, a Los Angeles Times investigation found that in a number of recent L.A. County deaths that were initially thought to be caused by kratom or 7-OH, there wasn’t enough evidence to say those drugs alone caused the deaths; it might be the case that the danger is in mixing them with other substances.

Meanwhile, the actual application of this new policy seems to be piecemeal at best.

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The county Public Health Department told The Times it conducted 2,696 kratom-related inspections between Nov. 10 and Jan. 27, and found 352 locations selling kratom products. The health department said the majority stopped selling kratom after those inspections; there were nine locations that ignored the warnings, and in those cases, inspectors impounded their kratom products.

But the reality is that people who need kratom will buy it on the black market, drive far enough so they get to where it’s sold legally or, like Wallace, order it online from a different state.

For now, retailers who sell kratom products are simply carrying on until they’re investigated by county health inspectors.

Ari Agalopol, a decorated pianist and piano teacher, saw her performances and classes abruptly come to a halt in 2012 after a car accident resulted in severe spinal and knee injuries.

“I tried my best to do traditional acupuncture, physical therapy and hydrocortisone shots in my spine and everything,” she said. “Finally, after nothing was working, I relegated myself to being a pain-management patient.”

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She was prescribed oxycodone, and while on the medication, battled depression, anhedonia and suicidal ideation. She felt as though she were in a fog when taking oxycodone, and when it ran out, ”the pain would rear its ugly head.” Agalopol struggled to get out of bed daily and could manage teaching only five students a week.

Then, looking for alternatives to opioids, she found a Reddit thread in which people were talking up the benefits of kratom.

“I was kind of hesitant at first because there’re so many horror stories about 7-OH, but then I researched and I realized that the natural plant is not the same as 7-OH,” she said.

She went to a local shop, Authentic Kratom in Woodland Hills, and spoke to a sales associate who helped her decide which of the 47 strains of kratom it sold would best suit her needs.

Agalopol currently takes a 75-milligram dose of mitragynine, the primary alkaloid in kratom, when necessary. It has enabled her to get back to where she was before her injury: teaching 40 students a week and performing every weekend.

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Agalopol believes the county hasn’t done its homework on kratom. “They’re just taking these actions because of public pressure, and public pressure is happening because of ignorance,” she said.

During the course of reporting this story, Authentic Kratom has shut down its three locations; it’s unclear if the closures are temporary. The owner of the business declined to comment on the matter.

When she heard the news of the recent closures, Agalopol was seething. She told The Times she has enough capsules of kratom for now, but when she runs out, her option will have to be Tylenol and ibuprofen, “which will slowly kill my liver.”

“Prohibition is not a public health strategy,” said Jackie Subeck, executive director of 7-Hope Alliance, a nonprofit that promotes safe and responsible access to 7-OH for consumers, at the Feb. 18 Senate hearing. “[It’s] only going to make things worse, likely resulting in an entirely new health crisis for Californians.”

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There were 13 full-service public health clinics in L.A. County. Now there are 6

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There were 13 full-service public health clinics in L.A. County. Now there are 6

Because of budget cuts, the Los Angeles County Department of Public Health has ended clinical services at seven of its public health clinic sites.

As of Feb. 27, the county is no longer providing services such as vaccinations, sexually transmitted infection testing and treatment, or tuberculosis diagnosis and specialty TB care at the affected locations, according to county officials and a department fact sheet.

The sites losing clinical services are Antelope Valley in Lancaster; the Center for Community Health (Leavy) in San Pedro, Curtis R. Tucker in Inglewood, Hollywood-Wilshire, Pomona, Dr. Ruth Temple in South Los Angeles, and Torrance. Services will continue to be provided by the six remaining public health clinics, and through nearby community clinics.

The changes are the result of about $50 million in funding losses, according to official county statements.

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“That pushed us to make the very difficult decision to end clinical services at seven of our sites,” said Dr. Anish Mahajan, chief deputy director of the L.A. County Department of Public Health.

Mahajan said the department selected clinics with relatively lower patient volumes. Over the last month, he said, the department has sent letters to patients about the changes, and referred them to unaffected county clinics, nearby federally qualified health centers or other community providers. According to Mahajan, for tuberculosis patients, particularly those requiring directly observed therapy, public health nurses will continue visiting patients.

Public health clinics form part of the county’s healthcare safety net, serving low-income residents and those with limited access to care. Officials said that about half of the patients the county currently sees across its clinics are uninsured.

Mahajan noted that the clinics were established decades ago, before the Affordable Care Act expanded Medi-Cal coverage and increased the number of federally qualified health centers. He said that as more residents gained access to primary care, utilization at some county-run clinics declined.

“Now that we have a more sophisticated safety net, people often have another place to go for their full range of care,” he said.

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Still, the closures have unsettled providers who work closely with local vulnerable populations.

“I hate to see any services that serve our at-risk and homeless community shut down,” said Mark Hood, chief executive of Union Rescue Mission in downtown Los Angeles. “There’s so much need out there, so it always is going to create hardship for the people that actually need the help the most.”

Union Rescue Mission does not receive government funding for its healthcare services, Hood said. The mission’s clinics are open not only to shelter guests, up to 1,000 people nightly, but also to people living on the streets who walk in seeking care.

Its dental clinic alone sees nearly 9,000 patients a year, Hood said.

“We haven’t seen it yet, but I expect in the coming days and weeks we’ll see more people coming through our doors looking for help,” he said. “They’re going to have to find help somewhere.” Hood said women experiencing homelessness are especially vulnerable when preventive care, including sexual and reproductive health services, becomes harder to access.

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County officials said staffing impacts so far have been managed through reassignment rather than layoffs. Roughly 200 to 300 positions across the department have been eliminated amid funding cuts, officials said, though many were vacant. About 120 employees whose positions were affected have been reassigned; according to Mahajan, no one has been laid off.

The clinic closures come amid broader fiscal uncertainty. Mahajan said that due to the Trump administration’s “Big Beautiful Bill,” Los Angeles County could lose $2.4 billion over the next several years. That funding, he said, supports clinics, hospitals and community clinic partners now absorbing patients who previously went to the clinics that closed on Feb. 27.

In response, the L.A. County Board of Supervisors has backed a proposed half-cent sales tax measure that would generate hundreds of millions of dollars annually for healthcare and public health services. Voters are expected to consider the measure in June.

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