Publisher Health

Working outdoors during periods of extreme heat can cause discomfort, heat stress, or heat illnesses — all growing concerns for people who live and work in Southwestern cities like Las Vegas, where summer temperatures creep higher each year. But, did you know that female outdoor workers are experiencing disproportionate impacts? Or, that more experienced outdoor workers are at higher risk than those with fewer years on the job?
In a new study in the International Journal of Environmental Science and Technology, scientists from DRI, Nevada State College, and the Guinn Center for Policy Priorities explore the growing threat that extreme heat poses to workforce health in three of the hottest cities in North America — Las Vegas, Los Angeles, and Phoenix. Their study results hold important findings for outdoor workers, their employers, and policymakers across the Southwestern U.S.
To assess the relationship between extreme heat and nonfatal workplace heat-related illness, the study compared data on occupational injuries and illnesses for the years 2011-2018 with heat index data from Las Vegas, Los Angeles, and Phoenix. Heat index data combines temperature and humidity as a measure of how people feel the heat.
“We expected to see a correlation between high temperatures and people getting sick — and we found that there was a very clear trend in most cases,” said lead author Erick Bandala, Ph.D., assistant research professor of environmental science at DRI. “Surprisingly, this type of analysis hadn’t been done in the past, and there are some really interesting social implications to what we learned.”
First, the research team analyzed changes in heat index data for the three cities. They found a significant increase in heat index at two of the three locations (Phoenix and Las Vegas) during the study period, with average heat index values for June-Aug climbing from “extreme caution” in 2012 into the “danger” range by 2018. Over the same period, data from the Bureau of Labor and Statistics showed that the number of nonfatal heat-related workplace injuries and illnesses in each of the three states increased steadily, climbing from below the national average in 2011 to above the national average in 2018.
“Our data indicate that the increases in heat are happening alongside increases in the number of nonfatal occupational injuries across these three states,” Bandala said. “Every year we are seeing increased heat waves and higher temperatures, and all of the people who work outside in the streets or in gardens or agriculture are exposed to this.”
Next, the study team looked deeper into the data to learn about the number of male and female workers being affected by heat-related workplace injuries. At the beginning of the study in 2011, 26 to 50 percent of the people affected across the three states were female. By 2018, 42 to 86 percent of the people affected were female.

A team of UC Davis researchers has identified a protein in the cancer cell’s nucleus as a critical agent keeping Kaposi’s sarcoma-associated herpesvirus (KSHV) dormant and undetected by the body’s immune system. The virus, in the same family as Epstein-Barr virus, is linked to AIDS-related Castleman’s disease and multiple cancers, such as Kaposi sarcoma and primary effusion lymphoma.
The number of people infected with the virus varies around the world. Less than 10% of people in the U.S. are infected with KSHV, compared to 50% of the population in some parts of Africa. Not everyone with KSHV will develop Kaposi sarcoma. Those who do, generally have a weakened immune system due to HIV infection, organ transplant, being older or other factors.
The introduction of antiretrovirals to control HIV significantly reduced AIDS-related Kaposi sarcoma prevalence in Western countries; however, in sub-Saharan Africa, the disease continues to have a poor prognosis.
What keeps the Kaposi’s sarcoma-associated herpesvirus dormant?
When the virus enters a human cell, it causes a hidden infection in the nucleus. During this stage, the virus is latching onto parts of the cell’s chromosomes and not producing viral offspring.
A study published in Cell Reports looked at KSHV’s latent-lytic switch, a process in which the virus exits its dormancy state to replicate in the host cell. This replication phase, called the lytic cycle, ends with the disintegration of the cell and the release of the viruses, infecting neighboring cells.

Researchers identified a protein in the fluid that could boost the cognition of aging animals — and might lead to future treatments for people.Five years ago, Tal Iram, a young neuroscientist at Stanford University, approached her supervisor with a daring proposal: She wanted to extract fluid from the brain cavities of young mice and to infuse it into the brains of older mice, testing whether the transfers could rejuvenate the aging rodents.Her supervisor, Tony Wyss-Coray, famously had shown that giving old animals blood from younger ones could counteract and even reverse some of the effects of aging. But the idea of testing that principle with cerebrospinal fluid, the hard-to-reach liquid that bathes the brain and spinal cord, struck him as such a daunting technical feat that trying it bordered on foolhardy.“When we discussed this initially, I said, ‘This is so difficult that I’m not sure this is going to work,’” Dr. Wyss-Coray said.Dr. Iram persevered, working for a year just to figure out how to collect the colorless liquid from mice. On Wednesday, she reported the tantalizing results in the journal Nature: A week of infusions of young cerebrospinal fluid improved the memories of older mice.The finding was the latest indication that making brains resistant to the unrelenting changes of older age might depend less on interfering with specific disease processes and more on trying to restore the brain’s environment to something closer to its youthful state.“It highlights this notion that cerebrospinal fluid could be used as a medium to manipulate the brain,” Dr. Iram said.Turning that insight into a treatment for humans, though, is a more formidable challenge, the authors of the study said. The earlier studies about how young blood can reverse some signs of aging have led to recent clinical trials in which blood donations from younger people were filtered and given to patients with Alzheimer’s or Parkinson’s disease.But exactly how successful those treatments might be, much less how widely they can be used, remains unclear, scientists said. And the difficulties of working with cerebrospinal fluid are steeper than those involved with blood. Infusing the fluid of a young human into an older patient is probably not possible; extracting the liquid generally requires a spinal tap, and scientists say that there are ethical questions about how to collect enough cerebrospinal fluid for infusions.While there are theoretically other ways of achieving similar benefits — such as delivering a critical protein in the fluid that the researchers identified or making a small molecule that mimics that protein — those approaches face their own challenges.Jeffery Haines, a biochemist who has studied cerebrospinal fluid and multiple sclerosis at Mount Sinai Medical Center in New York, said that the study had elegantly identified how certain ingredients in the fluid might promote memory. But he said the general public’s appetite for anti-aging drugs was outpacing the science.“In general, people are looking for the Holy Grail of aging, and they think there is going to be a magical factor that’s being secreted that’s just going to reverse this thing,” he said. “I don’t think it’s that simple.”Cerebrospinal fluid made for a logical target for researchers interested in aging. It nourishes brain cells, and its composition changes with age. Unlike blood, the fluid sits close to the brain.But for years, scientists saw the fluid largely as a way of recording changes associated with aging, rather than countering its effects. Tests of cerebrospinal fluid, for example, have helped to identify levels of abnormal proteins in patients with significant memory loss who went on to develop Alzheimer’s disease. Scientists knew that there were also health-promoting proteins in cerebrospinal fluid, but identifying their locations and precise effects seemed out of reach.For one thing, scientists said, it was difficult to track changes in the fluid, which the body continuously replenished. And collecting it from mice while avoiding contaminating the fluid with even trace amounts of their blood was extremely challenging.“The field has lagged decades behind other areas of neuroscience,” said Maria Lehtinen, who studies cerebrospinal fluid at Boston Children’s Hospital and is the co-author of a commentary in Nature about the new mouse study. “Largely this is because of the technical limitations in studying a fluid that’s deep inside the brain, and that turns over continuously.”Dr. Iram was undaunted. She set about taking the liquid from 10-week-old mice, cutting above their necks and drawing out fluid from a tiny cavity near the back of the brain while trying not to puncture any blood vessels or poke the brain itself.When she was successful, Dr. Iram said, the result was about 10 microliters of cerebrospinal fluid — roughly one-fifth of the size of a drop of water. To collect enough for infusions, she had to do the procedure on many hundreds of mice, taming the technical challenges that Dr. Wyss-Coray had warned of by sheer force of repetition.“I like doing these types of studies that require a lot of perseverance,” Dr. Iram said. “I just set on a goal, and I don’t stop.”To infuse the young cerebrospinal fluid into old mice, Dr. Iram drilled a tiny hole in their skulls and implanted a pump below the skin on their upper backs. For comparison, a separate group of old mice was infused with artificial cerebrospinal fluid.A few weeks later, the mice were exposed to cues — a tone and a flashing light — that they had earlier learned to associate with shocks to their feet. The animals that had received the young cerebrospinal fluid infusion tended to freeze for longer, suggesting that they had preserved stronger memories of the original foot shocks.“This is a very cool study that looks scientifically solid to me,” said Matt Kaeberlein, a biologist who studies aging at the University of Washington and was not involved in the research. “This adds to the growing body of evidence that it’s possible, perhaps surprisingly easy, to restore function in aged tissues by targeting the mechanisms of biological aging.”Dr. Iram tried to determine how the young cerebrospinal fluid was helping to preserve memory by analyzing the hippocampus, a portion of the brain dedicated to memory formation and storage. Treating the old mice with the fluid, she found, had a strong effect on cells that act as precursors to oligodendrocytes, which produce layers of fat known as myelin that insulate nerve fibers and ensure strong signal connections between neurons.The authors of the study homed in on a particular protein in the young cerebrospinal fluid that appeared involved in setting off the chain of events that led to stronger nerve insulation. Known as fibroblast growth factor 17, or FGF17, the protein could be infused into older cerebrospinal fluid and could partially replicate the effects of young fluid, the study found.Even more strikingly, blocking the protein in young mice appeared to impair their brain function, offering stronger evidence that FGF17 affects cognition and changes with age.The study strengthened the case that breakdowns in myelin formation were related to age-associated memory loss. That is something of a departure from the longstanding focus on the fatty insulation in the context of diseases like multiple sclerosis.Some scientists said that knowing one of the proteins responsible for the effects of young spinal fluid could open the door to potential treatments based on that protein. At the same time, recent technological advances have brought scientists closer to observing changes in cerebrospinal fluid in real time, helping them “peel back the layers of complexity and mystery surrounding this fluid,” Dr. Lehtinen said.Still, scientists cautioned that those treatments would not materialize anytime soon. Among the difficulties are understanding what other proteins might be involved and figuring out how to harness their effects without causing separate problems.But Dr. Wyss-Coray said that the study filled a critical gap in the understanding of how the brain’s environment changes as people age.“The question is, ‘How can you maintain cognitive health until you die? How can you make the brain resilient to this relentless degeneration of the body?’” he said, “and what a growing number of studies show is that as we learn more about the aging process itself, maybe we can slow down aspects of aging and maintain tissue integrity or even rejuvenate tissues.”

The study from Surrey suggests that controlling blood sugar levels within the first year of diagnosis reduces the incidence of major cardiovascular events. Furthermore, the team also found that the more a patient’s blood levels varied 12-months after diagnosis, the more likely they were to experience dangerous cardiovascular events.
Dr Martin Whyte, co-author of the study and Reader in Metabolic Medicine at the University of Surrey, said:
“The conventional wisdom has been to slowly and steadily treat type 2 diabetes with diet and medicine dose-escalation over years — the period over which it took people to reduce their sugar levels after diagnosis was thought less important for major vascular protection. However, our observational study suggests that getting blood levels under control quickly — within the first 12 months after diagnosis — will significantly help reduce cardiovascular events.”
Type 2 diabetes is a common condition that results in the level of sugar in the blood becoming too high. The condition is linked to obesity or a family history of type 2 diabetes and can increase a person’s risk of getting serious health conditions.
The University of Surrey’s study used Royal College of General Practitioners’ Research and Surveillance Centre database to perform a comprehensive examination of glycaemic control achieved within the first year of diagnosis and subsequent blood sugar level variability with cardiovascular disease incidents.
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Materials provided by University of Surrey. Note: Content may be edited for style and length.

Why are older adults more likely to get seriously ill or even die from pneumonia? It turns out the cause may have as much to do with the gut as it does with the lungs.
That’s according to new research from Rachel McMahan, PhD, assistant research professor of GI, trauma, and endocrine surgery in the University of Colorado School of Medicine, and CU School of Medicine immunology graduate student Holly Hulsebus.
In a paper published in March in the journal Frontiers in Aging, the researchers — along with senior author Elizabeth J. Kovacs, PhD, professor of GI, trauma, and endocrine surgery — looked at the bacteria Streptococcus pneumoniaein in animal models, studying changes in intestinal microbial populations after infection.
“Streptococcus pneumoniaeis normally carried in the nasal passages of healthy adults. People with healthy immune systems can just live with it, and it doesn’t cause any problems,” Hulsebus explains. “But people with compromised immune systems, including older adults, tend to become more susceptible because their immune system can’t really control the bacteria that are normally there. Those bacteria can leave the nose and move to other places in the body. They can cause ear infections, and they also can spread to the lungs and cause pneumonia.”
The role of the leaky gut
In addition to increased morbidity and impaired lung function after a Streptococcus pneumoniaeinfection in older mice, the researchers also found elevated levels of gut-derived bacteria in the lungs, suggesting that bacteria that migrate from the intestine to the lungs may partially be responsible for the poor outcomes in older individuals.

A new method blocks the protein regulation of the parasite Toxoplasma gondii and causes it to die off inside the host cell.
Toxoplasmosis is one of the most widespread zoonoses worldwide. It is an infectious disease that can be transmitted from cats to humans. People can also become infected by consuming raw or undercooked meat. Infection is particularly dangerous for pregnant women, as it can cause fetal deformities.
The cause of the disease is the single-celled parasite Toxoplasma gondii. Inside the host cell, it forms a little bubble-like compartment called a parasitophorous vacuole, which facilitates nutrient exchange and synchronized cell division. The resulting daughter cells are connected with each other inside the vacuole via a network, somewhat akin to an umbilical cord. Up to 64 daughter cells can form in the compartment. As soon as the offspring are mature, a regulation mechanism prompts the dissolution of the vacuole and the structures that have formed inside it. This is the moment at which the daughter cells become mobile and invade new host cells.
Hope for the development of new drugs
Before now, it was not known which genes encode the proteins that control the exit from the host cell. To identify them, a team led by Prof. Markus Meißner, Chair of Experimental Parasitology at LMU, collaborated with colleagues from the University of Glasgow in Scotland to develop a novel genetic screening technique, which is based on the Cas9 “genetic scissors,” and investigate a library of 320 parasite-specific genes. They discovered two genes without which cell egress is impossible.
The targeted destruction of these genes led to a blockade of the egress and thus to the death of the next generation of parasites within the host cell. “This paves the way potentially for the development of active substances that could block the function of the corresponding proteins and so put a halt to propagation,” observes Markus Meißner.
Toxoplasma gondii is closely related to the malaria pathogen Plasmodium falciparum. Therefore, the parasite serves as a model organism for the pathogen of the tropical disease, which kills hundreds of thousands of people worldwide every year. “We assume that similar processes control the propagation of the malaria pathogen,” explains LMU parasitologist Dr. Elena Jimenez-Ruiz. “Next, we will investigate what functions these proteins have in the malaria pathogen and whether there are possible starting points for the development of new drugs.”
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Materials provided by Ludwig-Maximilians-Universität München. Note: Content may be edited for style and length.

Many doctors caution their pregnant patients to avoid cat feces; even the family pet’s litter box is off-limits. Now, a group of researchers from Clemson University have discovered a promising therapy for those who suffer from toxoplasmosis, a disease caused by the microscopic protozoa Toxoplasma gondii.
T. gondii is the reason pregnant women are warned not to come in contact with cat feces. The Clemson team has enlisted an unlikely ally — the herbicide oxadiazon — in the fight against the single-celled parasite. The team hit on oxadiazon because of the herbicide’s ability to short-circuit the production of an enzyme that T. gondii needs to thrive.
Associate Professors Daniel Whitehead and Zhicheng Dou and former graduate student Kerrick Rees conducted the study. The journal ACS Infectious Disease, an American Chemical Society publication, published their findings in a paper titled, “Oxadiazon Derivatives Elicit Potent Intracellular Growth Inhibition against Toxoplasma gondii by Disrupting Heme Biosynthesis.”
T. gondii infects nearly all warm-blooded animals, including about one-third of all humans, making it one of the most widespread parasitic organisms known to humans, the researchers said. Humans can contract T. gondii in a number of ways, including eating certain undercooked, contaminated meats, especially pork, lamb and venison; contact with cat feces; and in the womb, if the mother is infected.
“Infections during pregnancy can be quite dangerous for women and their unborn babies, particularly in the first trimester,” said Whitehead, an associate professor in the Department of Chemistry.
When transmitted during pregnancy, the disease can cause birth defects and even fetal death. Toxoplasma infections can cause severe, even fatal complications in immunocompromised patients, such as people living with HIV and those undergoing chemotherapy.

Surgeons who observe persistent fluid buildup after disconnecting epileptic and healthy brain areas should think twice before installing low-pressure nonprogrammable drainage shunts, according to a study co-authored by Rutgers pediatric and epilepsy neurosurgeon Yasunori Nagahama that found chronic headaches could result from these procedures.
The study in Operative Neurosurgery followed 70 children who underwent a connection-severing surgery known as functional hemispherotomy for intractable epilepsy between 1994 and 2018 to see if inserting permanent drainage shunts after surgery increased the brain’s tendency to shift across the skull after surgery.
Epilepsy afflicts about 3.4 million Americans, according to the Centers for Disease Control. Various surgeries can help the 1 million people whose seizures can’t be controlled by medication. Hemispherotomy often eliminates seizures in juvenile patients whose epilepsy affects one side (or hemisphere) of the brain by removing some tissue and severing connections between the healthy and overactive hemispheres. However, tissue removal reduces local pressure, causing the remaining brain tissue to shift toward the low-pressure zone. This shift can cause persistent headaches and other problems.
The study is the first to examine whether shunts, which allow excess cerebrospinal fluid to drain into the abdominal cavity, increase brain shift and, if so, whether certain types of shunts increase it more than others.
The study’s initial measurements of average midline brain shift were comparable in shunted and nonshunted patients, but final measurements were 16.3 millimeters in shunted kids and 9.7 millimeters in nonshunted kids. Further investigation by Nagahama and colleagues from the University of California, Los Angeles suggests insufficient pressure in some shunt opening valves created the increased brain shift.
Patients whose shunts required above-average pressure to open their valves and drain fluid fared comparably to nonshunted patients. Patients whose shunts had below-average valve opening pressure experienced an average brain shift of 18.7 millimeters. Researchers also found that nonprogrammable shunt valves were associated with elevated brain shift — 18.9 millimeters — while programmable valves weren’t.
“The finding that shunts as a whole increase midline brain shift is interesting but not actionable,” said Nagahama, the director of pediatric epilepsy surgery at Rutgers University’s Robert Wood Johnson Medical School. You have to install shunts when there’s chronic cerebrospinal fluid buildup.”
“The second finding — that some types of shunts were associated with increased brain shift while others were not — is certainly an area for further research and possibly something for surgeons to consider in choosing shunts for this patient population,” the assistant professor added.
Nagahama said the study findings make intuitive sense. The brain naturally shifts from high-pressure areas to low-pressure areas until the pressure equalizes. Removing fluid further reduces pressure in an area that’s already missing brain tissue and thus increases brain shift. Shunts with valves that only open at higher pressures reduce the pressure differentials and reduce brain shift.
“Efforts to reduce brain shift should naturally focus on reducing pressure differences across the brain cavity,” said Nagahama, who specializes in epilepsy surgeries, including functional hemispherotomy.
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Materials provided by Rutgers University. Original written by Andrew Smith. Note: Content may be edited for style and length.

One of the most common causes of disability or death in newborns is a lack of oxygen or blood flow in the brain during labor or delivery.
The condition, known as hypoxic-ischemic encephalopathy (HIE), can result in severe brain damage, which is why researchers at the Case Western Reserve University School of Medicine and UH Rainbow Babies & Children’s Hospital (UH Rainbow) are studying the condition to evaluate how HIE is treated and develop new, more effective options.
HIE, usually caused by complications with the umbilical cord, uterine tearing, blood circulation problems in the placenta and more, can result in lifelong disabilites. Currently, the only treatment for HIE is hypothermia, or lowering the infant’s body temperature to reduce the metabolic rate and inflammation in the brain.
But according to new research from Case Western Reserve and UH Rainbow Babies and Children’s Hospital published in Pediatric Research, this approach doesn’t reverse brain damage caused by HIE.
“Hypothermia reduces the brain injury, but does not cure the baby,” said senior author Cynthia Bearer, MD, PhD, professor at the School of Medicine and chief of Neonatology at UH Rainbow. “We are studying why the HIE injury remains after hypothermia because it did not reverse the damage. It’s a common condition that affects between 1 and 3 out of every 1,000 infants.”
During infant brain development, many processes rely on the function of lipid rafts — components of cell membranes that act as messengers to bring proteins together and signal cell behavior. The research team believed that, because lipid rafts play a critical role in brain development, they may also hold the answer to reverse brain damage caused by HIE.
By examining lipid rafts in rat models, the researchers found an increase in the percentage of a protein called L1 cell adhesion molecule. This increase was found in both sides of the brain cerebellum. The cerebellum plays a large role in developing motor, cognitive and emotional functions in babies.
“The proportion of the protein in lipid rafts increased by seven-fold in some cases. These changes persisted after hypothermia,” said Bearer, who is also the William and Lois Briggs Chair in Neonatology. “The same increase in the proportion of L1 protein in lipid rafts occurred even when the research models were not treated by hypothermia, which shows hypothermia did not reverse this effect of HIE.”
Bearer said their findings show that hypothermia alone is not an effective treatment for reversing the effects of HIE and supports the team’s rationale that lipid rafts may be a target for more effective treatment.
For example, the researchers say one possible intervention strategy worth further study could be dietary, specifically focusing on a nutrient called choline. Choline is found in some foods, especially egg yolks, and plays a key role in brain development and lipid rafts.
“This study is the first of its kind to look at lipid rafts and their involvement in HIE,” Bearer said. “I am encouraged that these results will lead to more effective interventions to prevent brain injury.”
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New data show a surge in overdose deaths involving fentanyl and methamphetamine; overall, the nation saw a 15 percent increase in deaths from overdoses in 2021.WASHINGTON — Deaths from drug overdoses continued rising to record-breaking levels in 2021, nearing 108,000, according to preliminary new data published on Wednesday by the Centers for Disease Control and Prevention.The increase of nearly 15 percent followed a much steeper rise of almost 30 percent in 2020, an unrelenting crisis that has consumed federal and state drug policy officials. The number of drug overdose deaths has increased every year but 2018 since the 1970s.A growing share of deaths came from overdoses involving fentanyl, a class of potent synthetic opioids that are often mixed with other drugs, and methamphetamine, a synthetic stimulant. State health officials battling an influx of both drugs said many of the deaths appeared to be the result of combining the two.Drug overdoses, which long ago surged above the country’s peak deaths from AIDS, car crashes and guns, killed about a quarter as many Americans last year as Covid-19.Deaths involving synthetic opioids — largely fentanyl — rose to 71,000 from 58,000, while those associated with stimulants like methamphetamine, which has grown cheaper and more lethal in recent years, increased to 33,000 from 25,000. Because fentanyl is a white powder, it can be easily combined with other drugs, including opioids like heroin, and stimulants like meth and cocaine, and can be stamped into counterfeit pills for anti-anxiety drugs like Xanax. Such mixtures can prove lethal if drug users are unaware they are using fentanyl or are unsure of the dose.Deaths from both classes of drugs have been rising in recent years.But there is growing evidence that mixing stimulants and opioids — into combinations known as “speedballs” and “goofballs” — is growing more common, too. Dan Ciccarone, a professor of family and community medicine at the University of California, San Francisco, who studies drug markets, has just begun a multiyear study of the combination of opioids and meth.“There’s an intertwined synthetics epidemic the likes of which we’ve never seen,” he said. “We’ve never seen a powerful opioid such as fentanyl being mixed with such a potent methamphetamine.”The Opioid CrisisFrom powerful pharmaceuticals to illegally made synthetics, opioids are fueling a deadly drug crisis in America.Origins of an Epidemic: Purdue Pharma knew OxyContin was widely misused, but continued to promote the painkiller as less addictive.A Settlement: Purdue Pharma reached a deal with a group of states that long resisted the structure of the original bankruptcy plan. Here is what the agreement means.Detailing Tragedies: As part of the settlement, families who lost loved ones to opioid addiction were allowed to address the owners of Purdue Pharma in court.How Opioids Work: Through interviews with users and experts, we created a visual representation of how these drugs hijack the brain.A Pandemic Spike: As Covid raged, so did the opioid epidemic, causing overdose deaths in the U.S. to surge to a record high.The numbers released Wednesday are considered provisional, and may change as the government reviews more death records. But they added more definition to a crisis that has escalated sharply during the pandemic. The White House in recent weeks announced President Biden’s first national drug control strategy, and a plan to combat meth use, unveiled last week by his drug czar, Dr. Rahul Gupta, the first medical doctor to oversee the White House Office of National Drug Control Policy. Overdose deaths involving meth almost tripled between 2015 and 2019 in people 18 to 64, according to the National Institutes of Health.Mr. Biden is the first president to embrace harm reduction, an approach that has been criticized by some as enabling drug users, but praised by addiction experts as a way to keep drug users alive while providing access to treatment and support.Instead of pushing abstinence, the approach aims to lower the risk of dying or acquiring infectious diseases by offering sterile equipment — through needle exchanges, for example — or tools to check drugs for the presence of fentanyl. Strips that can detect fentanyl have become increasingly valuable resources for local health officials, and some states have moved recently to decriminalize them, even as others resist.The causes of the continued increase in overdoses are complex and hard to untangle, experts said. But state health officials and some addiction experts said the spike in overdoses, which began before the pandemic, could not be blamed solely on the disruptions that came with it, or on a major increase in the number of Americans using drugs.Social isolation and economic dislocation, which have been widespread during the pandemic, do tend to cause relapses in drug use, and could have contributed to rising overdoses. Shutdowns early in 2020 also caused some addiction treatment providers to temporarily close their doors. But the pandemic alone does not explain the recent trend.Policy changes made during the pandemic may have helped prevent more deaths. Regina LaBelle, an addiction policy expert at Georgetown University, said that early research has found that loosening rules to permit take-home methadone treatment had been beneficial, along with an increase in treatment via telemedicine.“The difference in what we’re seeing now is not how many people are using,” said Dr. Anne Zink, the chief health official in Alaska, which saw the largest overdose death percentage increase of any state in the nation, according to the data released on Wednesday.Instead, she said, the fentanyl supply had skyrocketed, in shipments that were difficult to track, penetrating even the most isolated parts of the state. Of the 140 fentanyl overdose deaths the state recorded in 2021, over 60 percent also involved meth, and nearly 30 percent involved heroin.Drug overdoses, which long ago surged above the country’s peak deaths from AIDS, car crashes and guns, killed about a quarter as many Americans last year as Covid-19.Spencer Platt/Getty ImagesFentanyl, which is made in a lab, can be cheaper and easier to produce and distribute than heroin, enhancing its appeal to dealers and traffickers. But because it is strong and sold in varying formulations, small differences in quantity can mean the difference between a drug user’s usual dose and one that proves deadly. It is particularly dangerous when it is used unwittingly by drug users who do not usually take opioids. The spread of fentanyl into a ever-growing portion of the nation’s drug supply has continued to flummox even states with strong addiction-treatment services.Often synthesized in Mexico from precursor chemicals made in China, fentanyl long ago permeated the heroin markets of the Northeast and Midwest. But recent data shows it has established a strong hold in the South and West as well.“The economics of fentanyl have just been pushing the other drugs out of the market,” said Dr. Joshua Sharfstein, a vice dean of the Bloomberg School of Public Health at Johns Hopkins University. “It’s just so cheap to buy fentanyl and turn around and put it in whatever.”A recent study of illicit pills seized by drug enforcement authorities found that a substantial share of what is marketed as OxyContin, Xanax or the attention deficit hyperactivity disorder drug Adderall now contains fentanyl. The spread of these counterfeit pills may explain a recent sharp increase in overdose deaths among teenagers, who are less likely to inject drugs than older people.Pat Allen, the Oregon Health Authority director, said that, as was the case in other states with surging overdose deaths, the clear difference in 2021 had been the ubiquity of fentanyl. Children as young as 12 are considered at high risk of obtaining counterfeit pills containing fentanyl, he said, and high schoolers are overdosing on them, believing they are opioid painkillers or anti-anxiety medication. The state was working to send naloxone tool kits to schools, similar to a program it has used in fast food restaurants, where people were overdosing in bathrooms.Mr. Allen said he had seen an alarming phenomenon among those who overdose: They perceive the risk of fentanyl to be low, even though the actual risk is “gravely higher.”“We’ve had an addiction issue in Oregon which we’ve known about for a long time,” he said. “This takes that existing addiction issue and makes it much more dangerous.”In 2021, overdoses amounted to one of the leading causes of death in the United States, similar to the number of people who died from diabetes and Alzheimer’s disease, and roughly a quarter of the number of people who died from Covid-19, the third leading cause of death, according to the C.D.C.In Vermont, 93 percent of opioid deaths in 2021 were fentanyl-related, according to Kelly Dougherty, the state’s deputy health commissioner.“In the beginning stages of the pandemic, we were attributing the increase to life being disrupted,” she said. But now, she added, a different explanation seems clear: “What is really the primary driver is the presence of fentanyl in the drug supply.”The state’s celebrated “hub and spoke” model of addiction treatment and its aggressive use of medication-assisted treatment programs, she said, were not enough to contend with the ease and speed with which people overdose on fentanyl.“You can have the most robust treatment system,” she said, “and not everybody is going to avail themselves of it when maybe they should, or before they end up overdosing.”And fentanyl is showing up in counterfeit pills, Ms. Dougherty said, including in OxyContin.She said Vermont officials had taken up new public messaging regarding fentanyl.“Just assume that it’s everywhere,” she said.