Publisher Health

Kenyan patients who spend more than three days in the nation’s hospitals are more likely to harbor a form of bacteria resistant to one of the most widely used antibiotic classes, according to a recent study led by Washington State University.
The research team found that 66% of hospitalized patients were colonized with bacteria resistant to third-generation cephalosporins, compared to 49% among community residents. Third-generation cephalosporins are typically used for serious infections, and resistance to these antibiotics leaves limited options for treating patients with some bacterial infections.
The study, published in the Clinical Infectious Diseases journal, was part of a pair of projects in Kenya and a third in Guatemala to determine the prevalence of antibiotic-resistant bacteria. The research also aimed to identify risk factors for colonization with bacteria resistant to important and frequently used classes of antibiotics, including third-generation cephalosporins.
“These bacteria can cause untreatable infections,” said Sylvia Omulo, an assistant professor at WSU’s Paul G. Allen School for Global Health who led the studies in Kenya. “We have to use surveillance to make sure we understand what causes these bacteria to colonize and, later, resist certain antibiotics.”
By examining health records of Kenyan hospital patients who were colonized with cephalosporin-resistant bacteria, researchers identified three risk factors associated with colonization. Those risk factors included hospitalization for more than three days at 132% increased risk, intubation at 73% and a positive HIV status at 70%.
A person colonized with the bacteria may show no symptoms of an infection; however, the germs are present and growing in their body, and the individual may be at increased risk of a more dangerous infection from something as simple as a minor medical procedure or sickness from common bacteria like E. coli and Klebsiella. The germs can unknowingly be spread through person-to-person contact or contaminated surfaces.

While resistance is often associated with improper antibiotic use, that does not appear to be a primary contributing factor for cephalosporin-resistant bacteria in either Kenya or Guatemala.
The Guatemala study, led by WSU Allen School assistant professor Brooke Ramay, was interrupted by the COVID-19 pandemic and resulted in data being collected during two time periods. Reported antibiotic use in the community declined three-fold between the pre- and post-periods, but the prevalence of cephalosporin-resistant bacteria remained steady, with colonization found in 67% of hospital patients and 46% of community subjects.
“If antibiotic use locally in the community was a major risk factor, we’d expect some change over the course of the year,” said WSU Regents Professor Douglas Call, corresponding author for the three publications.
In a Kenyan study of communities, the likelihood of colonization with cephalosporin-resistant bacteria rose by 12% with increasing visits to hospitals and clinics, and individuals who kept poultry were 57% more likely to have the resistant bacteria. Previous and ongoing work in both countries also highlights the role of bacterial transmission due to poor sanitation and hygiene.
What is not clear is if contact with the health care system is a source of transmission or if people seeking care are more likely to harbor these bacteria.
“We know if you’re interacting with the health care system, you’re more likely to carry these bugs, but we don’t know why yet,” Call said. “To sort out the cause from the effect, we need to track the same people over time and record how their colonization status changes with different behaviors. Studies to do this are being set up for the coming year.”
The research was completed in collaboration with the Centers for Disease Control and Prevention, University del Valle de Guatemala, University of Nairobi and the Kenya Medical Research Institute. The work was funded by the CDC and is part of the broader Antimicrobial Resistance in Communities and Hospitals (ARCH) study partnership, which has research projects in six countries. The most recent findings from WSU and other institutions involved in the ARCH study were published in a special supplement of the Clinical Infectious Diseases journal.

Children taking a prescription stimulant to manage symptoms of attention deficit hyperactivity disorder (ADHD) do not have more substance use or substance use disorder (SUD) as adolescents or young adults, according to a new study by researchers at the University of Pittsburgh School of Medicine.
Published today in JAMA Psychiatry, the study may provide some reassurance to parents and clinicians who may be hesitant to prescribe ADHD stimulant medications for fear that they may lay the groundwork for future substance use.
“Stimulants are the first-line treatment recommended for most individuals with ADHD — the drug class is an evidence-based treatment with few side effects,” said Brooke Molina, Ph.D., professor of psychiatry, psychology and pediatrics at Pitt. “Because stimulant medications are classified by the Drug Enforcement Administration as schedule two substances with the potential for misuse, many people fear that harmful substance use could result.”
ADHD is a neurobehavioral condition marked by chronic patterns of inattention, hyperactivity or impulsivity, or a combination of the three, that affects a person’s day-to-day functioning. Although ADHD can be managed with medication and other therapeutic approaches, it is a chronic condition that must be monitored throughout an individual’s life.
Molina and her colleagues assessed patients with ADHD over a 16-year period from childhood through adolescence to early adulthood to see if there was any association between stimulant treatment and subsequent substance use. The study conducted at Pitt is among the first to address the relationship between childhood use of prescription stimulants and later SUD by accounting for dozens of demographic, clinical and psychosocial factors that may predispose an individual to treatment and substance use.
“Our study not only accounted for age, but also used a statistical method that adjusted over time for the many characteristics that may distinguish treated from non-treated individuals,” said study co-author Traci Kennedy, Ph.D., assistant professor of psychiatry at Pitt. “Considering these factors allowed us to more accurately test the relationship between stimulants and substance use.”
While other studies have sought to uncover and define a possible connection between prescription stimulant use for ADHD and SUD, the association between the two has remained controversial. The results of some studies suggested a protective effect of prescription stimulant use on the risk of having SUD later in life, while others failed to find an association.
When factoring in age and other time-varying characteristics, such as household income, behavior problems and parental support, Pitt researchers found no evidence that prescription stimulant treatment in childhood provided protection against developing a SUD for adolescents or young adults with ADHD. However, researchers likewise did not find an association between stimulant use during childhood and increased substance misuse in the future
While some study participants self-reported an increase over time in heavy drinking, marijuana use, daily cigarette smoking and using other substances, an association with age was also found for stimulant treatment, with older participants being less likely to continue taking medication. When these trends were paired with rigorous statistical analysis, results provided no evidence that prolonged stimulant use is associated with reduced or increased risk for SUD.
“We hope the results of this study will help educate providers and patients,” Molina said. “By understanding that stimulant medication initially prescribed in childhood is not linked to harmful levels of substance use, I anticipate that parents’ and patients’ fears will be alleviated.”
Pitt researchers plan to study individuals who were first diagnosed with ADHD and treated with stimulants in adulthood. The study aims to learn if there are differences in the characteristics and outcomes of these adults compared to people who were diagnosed and first treated with stimulants in childhood.
Other authors of the study include Andrea Howard, Ph.D., of Carleton University, Canada; James Swanson, Ph.D., and Annamarie Stehli, M.P.H., both of the University of California, Irvine; L. Eugene Arnold, M.D., of The Ohio State University; John Mitchell, Ph.D., of Duke University; Edward Kennedy, Ph.D., of Carnegie Mellon University; Jeffery Epstein, Ph.D., of the University of Cincinnati; Lily Hechtman, M.D., of McGill University; Stephen Hinshaw, Ph.D., of the University of California, Berkley; and Benedetto Vitello, M.D., of the University of Turin, Italy.

Engineering T cells to destroy cancer cells has shown success in treating some types of cancer, such as leukemia and lymphoma. However, it hasn’t worked as well for solid tumors.
One reason for this lack of success is that the T cells target only one antigen (a target protein found on the tumors); if some of the tumor cells don’t express that antigen, they can escape the T cell attack.
MIT researchers have now found a way to overcome that obstacle, using a vaccine that boosts the response of engineered T cells, known as chimeric antigen receptor (CAR) T cells, and also helps the immune system generate new T cells that target other tumor antigens. In studies in mice, the researchers found that this approach made it much more likely that tumors could be eradicated.
“This vaccine boosting appears to drive a process called antigen spreading, wherein your own immune system collaborates with engineered CAR T cells to reject tumors in which not all of the cells express the antigen targeted by the CAR T cells,” says Darrell Irvine, the Underwood-Prescott Professor with appointments in MIT’s departments of Biological Engineering and of Materials Science and Engineering, and a member of MIT’s Koch Institute for Integrative Cancer Research and the Ragon Institute of MGH, MIT, and Harvard.
Irvine is the senior author of the study, which appears today in Cell. The lead author of the paper is Leyuan Ma, a former postdoc at the Koch Institute and currently an assistant professor of pathology and laboratory medicine at the University of Pennsylvania School of Medicine.
Engineered T cells
The U.S. Food and Drug Administration has approved several types of T cell treatments for blood cancers. These treatments are based on CAR-T cells, which are engineered to display receptors that can recognize a specific antigen found on cancer cells.

To try to adapt this kind of treatment to glioblastoma, a type of brain cancer, researchers have designed CAR-T cells that target a mutated version of the EGFR receptor. However, not all glioblastoma cells express this antigen, and when attacked by CAR-T cells, some glioblastoma cells respond by halting production of the target antigen.
In a 2019 study, Irvine and his colleagues enhanced CAR-T cells’ effectiveness against glioblastoma by delivering a vaccine to mice shortly after the engineered T cells were administered. This vaccine, which carries the same antigen targeted by the CAR-T cells, is taken up by immune cells in the lymph nodes, where the CAR-T cells are exposed to it.
In that study, the researchers found that this vaccine boost not only helped the engineered CAR-T cells attack tumors, but it had another, unexpected effect: It helped to generate host T cells that target other tumor antigens.
This phenomenon, known as “antigen spreading,” is desirable because it creates populations of T cells that, working together, can fully eradicate tumors and prevent tumor regrowth.
“That would be exactly the kind of thing that could help you deal with the antigen heterogeneity of solid tumors, because if you primed host T-cells to attack other antigens, they may be able to come in and kill the tumor cells that your CAR-T cells cannot,” Irvine says.

An immune boost
In their new study, the researchers wanted to explore how that additional T-cell response becomes activated. They used the same type of CAR-T cells from their 2019 study, which are engineered to target mutant EGFR, and the same vaccine. The mice in the study were given two doses of the vaccine, one week apart.
The researchers found that in these boosted mice, metabolic changes occurred in the CAR-T cells that increased their production of interferon gamma, a cytokine that helps stimulate a strong immune response. This helps the T cells to overcome the immunosuppressive environment of the tumor, which normally shuts down any T cells in the vicinity.
As the CAR-T cells killed tumor cells expressing the target antigen, host T cells (not the engineered CAR-T cells) encountered other antigens from those tumor cells, stimulating those host T cells to target those antigens and help destroy tumor cells.
Without that host T cell response, the researchers found, tumors would regrow even if the CAR-T cells destroyed most of the original tumor cells. This happens because tumor cells treated with CAR-T cells often stop producing the antigen targeted by the engineered cells, allowing them to evade those cells.
Tumor eradication
The researchers then tested their approach in mice with tumors that had different levels of the target antigen. They found that even in tumors where only 50 percent of the tumor cells expressed the target antigen, about 25 percent of the tumors could still be eradicated, by a combination of CAR-T cells and host T-cells.
The success rate was higher for tumors with greater levels of the target antigen. When 80 percent of the tumor cells expressed the antigen targeted by CAR-T cells, tumors were eliminated in about 80 percent of the mice.
The technology used in this study has been licensed to a company called Elicio Therapeutics, which is working on developing it for potential testing in patients. In this study, the researchers focused on glioblastoma and melanoma, but they believe it could potentially be used to combat other types of cancer as well.
“In principle, this should apply to any solid tumor where you have generated a CAR T-cell that could target it,” Irvine says.
The researchers are also working on ways to adapt CAR-T cell therapy so that it can be used to attack tumors for which no targetable antigens have been identified.
The research was funded by the National Institutes of Health, the Marble Center for Cancer Nanomedicine at the Koch Institute, an ASPIRE Award from The Mark Foundation for Cancer Research, an American Cancer Society postdoctoral fellowship, the Cell and Gene Therapy Collaborative at the Children’s Hospital of Philadelphia, the W.W. Smith Charitable Trust, and a Koch Institute Support (core) Grant from the National Cancer Institute.

With a new method for examining virus samples researchers from the University of Copenhagen have solved an old riddle about how Hepatitis C virus avoids the human body’s immune defenses. The result may have an impact on how we track and treat viral diseases in general.
An estimated 50 million people worldwide are infected with with chronic hepatitis C. The hepatitis C virus can cause inflammation and scarring of the liver, and in the worst case, liver cancer. Hepatitis C was discovered in 1989 and is one of the most studied viruses on the planet. Yet for decades, how it manages to evade the human immune system and spread through the body has been a riddle — one that Danish researchers have become the first to solve.
A new method for examining virus samples has led researchers at the University of Copenhagen and Hvidovre Hospital to the answer, which is: the virus just puts on a ‘mask’.
By donning a mask, the virus can remain hidden while making copies of itself to infect new cells. The mask cloaks the virus in the form of a molecule already in our cells. Disguised by the molecule, our immune systems confuse the virus with something harmless that needn’t be reacted to.
“How the Hepatitis C virus manages to hide in our liver cells without being detected by the immune system has always been a bit of a mystery. Our revelation of the virus’ masking strategy is important, as it could pave the way for new ways of treating viral infections. And it is likely that other types of viruses use the same trick,” says Associate Professor Jeppe Vinther of the Department of Biology, who together with associate professor Troels Scheel and professor Jens Bukh from Copenhagen Hepatitis C Program headed the research.
Camouflage for a malicious virus
The mask used by the hepatitis virus to hide in our cells is called FAD, a molecule composed of Vitamin B2 and the energy carrying molecule ATP. FAD is vital for our cells to convert energy. The FAD molecule’s importance and familiarity to our cells makes it ideal camouflage for a malicious virus.

For several years, the research team had a good idea that FAD was helping the virus hide in infected cells, but they lacked a clear way to prove it. To solve the challenge, they turned to Arabidopsis, a well-known experimental plant among researchers.
“We were getting desperate to find a way to prove our hypothesis, which is when we purified an enzyme from the Arabidopsis plant that can split the FAD molecule in two,” explains Anna Sherwood from Department of Biology, who together with Lizandro Rene Rivera Rangel are first authors of the study.
Using the enzyme, the researchers were able to split the FAD and prove that the hepatitis C virus used it as a mask.
Other viruses probably use the same trick
Like both the coronavirus and influenza virus, Hepatitis C is an RNA virus. Its genetic material consists of RNA that must be copied once the virus enters its host organism. New RNA copies are used to take over new cells, and one end of the RNA’s genetic material is masked by the FAD.
According to Jeppe Vinther, it is very realistic that other RNA viruses use similar masking techniques to spread without being detected by cellular control systems. In fact, researchers have already found another virus that uses the same strategy. And there are likely more.
“All RNA viruses have the same need to hide from the immune system and there is a good chance that this is just the beginning. Now that we’re attuned to this trick, it opens up the possibility of developing new and perhaps improved methods of tracking and treating viral infections in the future,” concludes Jeppe Vinther.
The research is funded by Independent Research Fund Denmark, as well as several other Danish and European foundations and conducted in a collaboration between Jeppe Vinther’s research group at the Department of Biology, University of Copenhagen, and Troels Scheel and Jens Bukh’s research groups from the Copenhagen Hepatitis C Program, which are located at UCPH’s Department of Immunology and Microbiology and the Department of Infectious Diseases at Hvidovre Hospital.

A study of the genetic variation that makes mice more susceptible to bowel inflammation after a high-fat diet has identified candidate genes which may drive inflammatory bowel disease (IBD) in humans. The findings are published as a Reviewed Preprint in eLife.
Described by the editors as a fundamental study, the work provides a framework for using systems genetics approaches to dissect the complex mechanisms of gut physiology. The authors show how it is possible to use genetically diverse but well-characterised mice to interrogate intestinal inflammation and pinpoint genes influenced by the environment – in this case, a high-fat diet – and identify potential treatment targets for IBD in mice and humans. The editors describe the strength of the analyses as compelling and add that, as a resource, it will be useful for linking genetic variations and diet to gut-related disorders.
It is well established that a high-fat diet can increase the risk of IBD. However, the impact of diet varies between individual people, suggesting an interplay with genetic factors. More than 200 risk genes have been identified for IBD, but there is still no effective treatment, and it is therefore important to understand the gene-by-environment interactions underpinning the inflammation that eventually evolves into IBD.
“Differences in the clinical presentation of IBD among patients, as well as diversity in diet and lifestyle, render human genetic studies challenging,” explains lead author Xiaoxu Li, a Doctoral Research Assistant at the Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Switzerland. “Genetically diverse populations of mice allow us to mirror the differences in human populations, while controlling several environmental factors, such as temperature and diet, when exploring the genetic modulators of IBD in the laboratory.”
Li and colleagues used mouse genetic reference populations (GRPs) to map the genetic factors that are important in IBD induced by a high-fat diet. They measured the levels of gene expression in the colons of 52 mice fed with either a chow or a high-fat diet and identified a subset of mice that were more susceptible to high-fat-diet-induced intestinal inflammation. Moreover, they found that levels of a pro-inflammatory cytokine called interleukin-15 were increased in the mice more likely to develop IBD, while levels of the anti-inflammatory cytokine, Interleukin-10, were decreased. This indicates that changes in the levels of genes associated with IBD reflect the general inflammatory status of mice.
After classifying different mouse strains based on their likelihood of developing IBD-like genetic signatures, the team explored this further using gene co-expression network analysis. This identified two distinct modules (clusters) of genes that are related to known genetic signatures of human IBD.
Next, they looked at the function of these genes and how they are controlled. Both IBD-associated modules largely consisted of immune response-related genes, including those known to be involved in Crohn’s disease, and the team identified the likely regulators of the expression of these genes. But the genetic drivers behind the different susceptibility in the mice were still elusive.
To find the candidate genes that influence gut inflammation specifically following a high-fat diet, they performed QTL analysis to identify quantitative trait loci (QTL) – regions of genes that interact with the environment to impact the observable trait data. This revealed a QTL that is related to chronic intestinal inflammation in mice.
To see whether genes under this QTL could play a role in human IBD, the team then cross-checked their findings with risk genes for IBD by conducting an analysis using genome-wide association study data from UK Biobank*. They identified two plausible gene candidates, called EPHA6 and MUC4. In addition, using publicly available genetic variation data for IBD, Crohn’s disease and ulcerative colitis, they found evidence to suggest that increased expression of the MUC4 gene in part of the colon may increase the risk of IBD in humans.
A limitation of this analysis is that there were no mechanistic investigations or studies that directly provide a causative link between the candidate genes and IBD. The results are primarily observational and correlative, but they provide a dataset that generates hypotheses that can be studied further.
“Our results point to important potential roles of two gene candidates in gut chronic inflammation that may lead to inflammatory disorders,” says senior author Johan Auwerx, a Professor at the Institute of Bioengineering, EPFL. “Our systems genetics approach using GRP mice where the genetic backgrounds are known and the environment can be controlled enables the prioritisation of candidate genes in a complex disease which, when combined with human genome-wide association studies from UK Biobank, are generalisable to human patients and may have clinical value.”

Georgetown University Medical Center neuroscientists say the brain’s auditory lexicon, a catalog of verbal language, is actually located in the front of the primary auditory cortex, not in back of it — a finding that upends a century-long understanding of this area of the brain. The new understanding matters because it may impact recovery and rehabilitation following a brain injury such as a stroke.
The findings appear in Neurobiology of Language on July 5, 2023.
Riesenhuber’s lab showed the existence of a lexicon for written words at the base of the brain’s left hemisphere in a region known as the Visual Word Form Area (VWFA) and subsequently determined that newly learned written words are added to the VWFA. The present study sought to test whether a similar lexicon existed for spoken words in the so-called Auditory Word Form Area (AWFA), located anterior to primary auditory cortex.
“Since the early 1900s, scientists believed spoken word recognition took place behind the primary auditory cortex, but that model did not fit well with many observations from patients with speech recognition deficits, such as stroke patients,” says Maximilian Riesenhuber, PhD, professor in the Department of Neuroscience at Georgetown University Medical Center and senior author of this study. “Our discovery of an auditory lexicon more towards the front of the brain provides a new target area to help us understand speech comprehension deficits.”
In the study, led by Srikanth Damera, MD, PhD, 26 volunteers went through three rounds of functional magnetic resonance imaging (fMRI) scans to examine their spoken word processing abilities. The technique used in this study was called functional-MRI rapid adaptation (fMRI-RA), which is more sensitive than conventional fMRI in assessing representation of auditory words as well as the learning of new words.
“In future studies, it will be interesting to investigate how interventions directed at the AWFA affect speech comprehension deficits in populations with different types of strokes or brain injury,” says Riesenhuber. “We are also trying to understand how the written and spoken word systems interact. Beyond that, we are using the same techniques to look for auditory lexica in other parts of the brain, such as those responsible for speech production.”
Josef Rauschecker, PhD, DSc, professor in the Department of Neuroscience at Georgetown and co-author of the study, adds that many aspects of how the brain processes words, either written or verbal, remain unexplored.
“We know that when we learn to speak, we rely on our auditory system to tell us whether the sound we’ve produced accurately represents our intended word,” he said. “We use that feedback to refine future attempts to say the word. However, the brain’s process for this remains poorly understood — both for young children learning to speak for the first time, but also for older people learning a second language.”

A research group from Japan has developed a method to produce highly active mRNA vaccines at high purity using a unique cap to easily separate the desired capped mRNA. This ‘Purecap’ technique extracted up to 100% pure Cap2-type mRNA, which showed 3-4 times better production of the protein that stimulates the immune system. These results open up the possibility of purer vaccines with a lower risk of inflammation caused by impurities. Their findings were published in Nature Communications.
mRNA vaccines have been used successfully as therapy against variants of the coronavirus. This has given researchers hope for their future use as a cancer vaccine. However, the purity of vaccines hinders this goal because impurities can trigger the immune system. This may cause inflammation around the injection site, a common side effect of vaccination.
Impurities in mRNA vaccines are often introduced in the capping stage. During this stage, a cap structure is added that improves the translation of mRNA and protects and stabilizes it. Caps can only be added to single-stranded mRNA, so ideally a vaccine should contain 100% pure single-stranded mRNA. However, unwanted double-strands of mRNA may be present, reducing its purity.
As single- and double-stranded mRNAs have different properties, they can be separated using a technique called reversed-phase high-performance liquid chromatography (RP-HPLC). This technique separates mRNAs on the basis of their hydrophobicity or hydrophilicity, i.e., their repulsion to or attraction to water.
A research group led by Professor Hiroshi Abe (he, him), Project Assistant Professor Masahito Inagaki (he/him), and Project Associate Professor Naoko Abe (she, her) of the Graduate School of Science, Nagoya University, in collaboration with Tokyo Medical and Dental University, used a unique PureCap method to introduce a hydrophobic tag at the capping stage. The tagged mRNA was easily separated at the RP-HPLC stage. The tag was then easily removed by light treatment, resulting in a 98%-100%-pure vaccine.
“We were very excited about the result when we saw on the chart that the RP-HPLC process had separated completely the capped and uncapped RNAs,” Hiroshi Abe said. “For a coronavirus mRNA, which is 4247 bases long, we successfully used the PureCap method to produce capped mRNA with over 98% purity.”
The research group paid particular attention to a group of cap structures that exist in animal and plant cells, called Cap0, Cap1, and Cap2. Although Cap2 is found in animal and plant cells, the evaluation of its function has been difficult because there was no way to obtain pure capped mRNA to ensure a fair test.
“The Cap structure used in mRNA vaccines has so far been limited to Cap0 and Cap1 types. However, we used our technique to manufacture Cap0, Cap1, and Cap2-type structures,” Abe said. “Highly purified Cap0, Cap1, and Cap2-type mRNA synthesized using the PureCap method showed lower immunostimulatory activity compared to mRNAs synthesized using conventional techniques showing their potential use in pharmaceuticals.”
As viruses mostly produce Cap1 mRNA, the immune system is less stimulated by Cap2. This suggests that a vaccine that uses Cap2 would be less likely to cause unwanted side effects such as inflammation when it is injected. However, it would still be able to create viral proteins when transcribed that make the vaccine effective.
The group used Purecap to create Cap2 mRNA and analyzed its protein synthesis capacity. They found that Cap2 mRNA produced 3-5 times more protein than Cap1 mRNA, which would enhance the immune response. They also showed that their Cap2-type mRNAs caused lower stimulation of the inflammatory response than mRNAs synthesized using conventional techniques.
“Conventional mRNA vaccine production methods could not prepare capped mRNA with high purity, raising concerns about reduced protein synthesis and impurity-derived inflammatory reactions,” Abe said. “The PureCap method solves these problems by selectively purifying only capped mRNA. Furthermore, the Cap2-type structure created using this technique is more efficient in protein synthesis and less irritating to the immune system. This technique has the potential to improve the safety and efficacy of mRNA vaccines. It is a revolutionary advance toward the practical application of mRNA medicine, as well as deepening our understanding of the fundamentals of mRNA science.”

Fish consumption has long been associated with numerous health benefits. However, it is also the main dietary source of toxic mercury in humans. A year-round study from a Finnish boreal lake shows that mercury concentration in some fishes is significantly higher in winter and near spring spawning and lowest in autumn after the growing season.
The pronounced seasonal changes of warm open-water and cold ice-covered seasons dominate natural cycles in Finnish lakes.
“Summer is the growing season of fish followed by weight loss during winter and spring spawning time” says research team leader, Professor Kimmo Kahilainen from the Lammi Biological Station, University of Helsinki.
Significant changes in temperature and other environmental factors during colder months result in lowered metabolism in fish. Additionally, less food is available for fish during this harsh timeframe. Under these conditions, eventually the energy required to grow is not met by the amount of energy taken in, resulting in weight loss and starvation.
This seasonal cycle means that fish mercury in winter and spring can be up to 30-40% higher compared to summer and autumn. Differences are pronounced in fish feeding on other fish, such as perch and pikeperch, which are important species for both recreational and commercial fishing in the boreal region and continue to be staples in regional dishes. Despite the higher mercury found during these seasons, all fish species in studied southern Finnish lake were below the fish consumption health limit (0.5 mg/kg) for mercury.
Winter is an immensely important driver of natural cycles, but how, and to what extent these colder months influence lake ecosystems is not well understood or just assumed, as minimal field research is conducted during this time of the year compared to warmer months. The nature of the work is demanding, requiring physically intensive and extended periods of time in freezing conditions on potentially unstable surfaces in low light. Such conditions present numerous logical challenges for researchers to contend with and manage effectively and responsibly.
Lead author doctoral researcher Alex Piro from the Lammi Biological Station, University of Helsinki, suggests that “considering our findings in perch and pikeperch, more frequent boreal mercury monitoring in wild fish during winter should be considered due to their higher concentration. When considering the human nutrition and fisheries management perspectives, the sustainable solution would be to consider limiting the fishing near the spawning time.”
This study conducted at the University of Helsinki Lammi Biological Station provides valuable insights into the seasonal dynamics of mercury in fish, contributing to ongoing efforts to accurately monitor and understand mercury levels in fish and support informed decision-making.

This fall, Americans will be urged to get shots against the flu, Covid and, if they’re older, R.S.V.To prevent a repeat of last winter’s “tripledemic” of respiratory illnesses, Americans will be encouraged to roll up their sleeves not just for flu shots but for two other vaccines, one of them entirely new.Federal health officials have already asked manufacturers to produce reformulated Covid vaccines to be distributed later this year. Recently, the Centers for Disease Control and Prevention took an additional step, endorsing two new vaccines against respiratory syncytial virus for older Americans.The three shots — flu, Covid and R.S.V. — may help to reduce hospitalizations and deaths later this year. But there are uncertainties about how the vaccines are best administered, who is most likely to benefit, and what the risks may be.For older and immunocompromised Americans, all three vaccines are a “godsend,” said Dr. Ofer Levy, director of the precision vaccines program at Boston Children’s Hospital and an adviser to the Food and Drug Administration.“The number of elders who die of viral infection every winter in our intensive care units, and also sometimes in the summer, is large — it’s in the tens of thousands of individuals,” Dr. Levy said. “Each of these vaccines is a huge win.”Yet it’s unclear how many Americans will opt for the shots. Some 71 percent of adults ages 65 and older got a flu shot this past winter, but only about 43 percent chose to get the Covid booster.The misery of the past winter may help change minds. The flu may have led to as many as 58,000 deaths, peaking in December, according to the C.D.C. Covid claimed roughly 50,000 lives between November and March.R.S.V. kills up to 10,000 people each year, most of them older. Infections this year peaked in November and resulted in about twice as many hospitalizations, including children, as in prepandemic years.Only the Covid and flu vaccines were available last fall. The R.S.V. vaccines for adults are new, and in clinical trials proved to be highly effective against infection of the lower respiratory tract, which includes the lungs.In May, the F.D.A. approved the first two versions, made by Pfizer and GSK, for older adults. The C.D.C.’s advisers recommend that Americans age 60 and older get the shot in consultation with their doctors. (The Pfizer vaccine is also being evaluated for use in pregnant women as a way to protect newborn infants.)Bundling all three inoculations into a single visit to a clinic or pharmacy is likely to encourage more people to get immunized, Dr. Levy said. “Plus, you want to get these shots in arms before the viral respiratory season in the winter,” he added.But other scientists hesitated to endorse the idea, citing the paucity of data on safety and effectiveness when all three are given at the same time.Pfizer’s new respiratory syncytial virus vaccine in production. In clinical trials, the shots proved highly effective against infection of the lower respiratory tract, which includes the lungs.Pfizer, via ReutersSometimes, vaccines work against one another when administered simultaneously. According to data presented to the C.D.C.’s advisers, the R.S.V. and flu vaccines produced lower levels of antibodies when given at the same time than when either was given alone.“I would say, when possible, it might be good to spread them out,” said Dr. Camille Kotton, a physician at Massachusetts General Hospital and a member of the C.D.C. scientific advisory panel.“I remain clinically concerned, especially where influenza vaccine doesn’t engender as much protection as we might like,” she said.The vast majority of people at risk for illness and death following infections with these viruses are those 75 and older. In that group, the benefit from each of the vaccines clearly outweighs any safety concerns, Dr. Kotton and other experts said.Up to 85 percent of flu-related deaths in recent years were among those age 65 and older, according to the C.D.C. The agency recommends that older adults get a high-dose flu vaccine or one with an adjuvant, an ingredient that can produce a stronger immune response.Hospitalizations and deaths from Covid also occur primarily in the oldest Americans, and Covid boosters are now thought to be beneficial primarily for older adults and people with weakened immune systems.In June, the F.D.A. advised Pfizer-BioNTech, Moderna and Novavax to manufacture Covid shots designed to target XBB.1.5, the Omicron variant that accounts for roughly 27 percent of cases. That variant seems to be receding, however, and a newer variant, XBB.1.16, is on the upswing.R.S.V. is the leading cause of infant hospitalizations in the United States, and among the top killers of young children in low- and middle-income countries. The virus was underappreciated as a respiratory threat to adults until recently. The virus may lead to as many as 160,000 hospitalizations and 10,000 deaths among older adults each year, according to the C.D.C. — and those numbers are likely to be underestimates. For every one million adults age 65 and older who get the vaccine, 25,000 outpatient visits, 2,500 hospitalizations and 130 deaths would be prevented, according to one analysis presented to the agency’s advisers.For decades, vaccines against R.S.V. proved challenging to design. A breakthrough in 2013 galvanized efforts by several companies. In a recent trial, the GSK vaccine, to be sold as Arexvy, retained much of its potency into the second year, and its efficacy is being studied for an even longer period.Pfizer is still evaluating the durability of its vaccine, which will be marketed as Abrysvo. If the vaccines remain effective over a long time, an R.S.V. shot may be not be needed every year.The companies’ trials did not enroll enough people who were immunocompromised, medically frail, live in long-term care facilities, or were 75 and older to gauge efficacy in those groups. These are also the Americans most vulnerable to R.S.V.Although flu and other vaccines carry a small risk of the autoimmune disease Guillain-Barré syndrome, those numbers generally are on the order of one or two cases per million. Evaluating the new R.S.V. vaccines, the manufacturers each reported three neurological cases, including Guillain-Barré syndrome, within 42 days of vaccination in a population of about 40,000 people.Still, the trials were not large enough to determine whether those cases occurred by chance or were caused by the vaccines. “That information really can’t be obtained until post licensure and post recommendation and rollout,” said Dr. Helen Chu, a physician and immunologist at the University of Washington.A drive-through testing site for coronavirus, flu and R.S.V. in Seattle.Lindsey Wasson/ReutersInfluenza, Covid and R.S.V. infections themselves pose a risk of Guillain-Barré syndrome and other neurological problems, so the risk-benefit balance still heavily favors vaccination, Dr. Chu said.Still, the reports of adverse events related to the R.S.V. vaccines made some C.D.C. advisers reluctant to back them for people who do not face high risks from the infection.That’s partly why the scientific panel said that anyone age 60 and older “may” opt to get the vaccine in consultation with a doctor, instead of issuing a blanket recommendation for all adults over 60 or even 65.That decision risks deepening racial inequities regarding vaccination, some experts said. Many people of color, often at disproportionate risk of severe illness or death, do not have easy access to a health care provider who might help them weigh the risks and benefits of R.S.V. vaccination.The recommendation also places the onus on general physicians and other health care providers to weigh the risks and benefits, Dr. Chu noted.“It’s hard for the committee,” she said, referring to the C.D.C.’s expert panel. “It’s certainly going to be much, much harder for a G.P.”The C.D.C.’s recommendations ensure that most Americans will not have to pay out of pocket for the vaccines. This fall marks the first time that the distribution of Covid vaccines will not be managed by the federal government, but insurance companies will continue to cover the costs.How much Pfizer and GSK will charge for the new R.S.V. vaccines is still unclear. Pfizer said the price of its vaccine was still being negotiated, but might fall between $180 and $270.GSK doubled its initial price of $148 two weeks before the C.D.C. advisers were scheduled to meet, giving the agency staff little time to redo its cost-effectiveness analysis, according to one C.D.C. scientist with knowledge of the matter. GSK now has settled on a range of $200 to $295.GSK raised its price because of the new data showing effectiveness into a second season, said Alison Hunt, a spokeswoman for the company.Ongoing research is likely to provide more information on the new R.S.V. vaccines. In preliminary data, a second dose of the GSK vaccine did not boost antibody levels, which puzzled the science advisers at last week’s meeting.Pfizer is investigating whether a second dose of its vaccine, given one year after the first, will boost immunity. Those results are expected some time early next year. The companies are also studying whether people who are immunocompromised should get a single dose or two doses given one month apart.“We never have all the information we want,” said Dr. Levy, the F.D.A. adviser.“But one thing we know for sure is that every winter people lose loved ones, grandmothers, grandfathers to the viruses, and now we have better tools. And we want to deploy them.”

Here’s who should get the flu, Covid and R.S.V. vaccines, and when.Most Americans have had one or more shots of the flu and Covid vaccines. New this year are the first shots to protect older adults from respiratory syncytial virus, a lesser-known threat whose toll in hospitalizations and deaths may rival that of flu.Federal health officials are hoping that widespread use of these three vaccines will head off another “tripledemic” of respiratory illnesses, like the one seen last winter. For people with insurance, all of the vaccines should be available for free.“This is an embarrassment of riches,” said Dr. Ofer Levy, director of the precision vaccines program at Boston Children’s Hospital and an adviser to the Food and Drug Administration.Here’s what he and other experts say about who should receive which vaccines, and when.What respiratory illnesses are coming our way?The coronavirus, flu and R.S.V. are all likely to resurge this fall, but exactly when and how much damage they will do are unknown. That’s in part because the restrictions in place during the pandemic altered the seasonal patterns of the viruses.This past winter, the flu peaked in December instead of in February, as it typically does. The virus may have caused as many as 58,000 deaths, a higher number than usual. Covid kept up a steady number of infections and deaths most of the season, with a peak in January.Compared with its pattern before the pandemic, R.S.V. peaked several weeks earlier last year, and it circulated for longer than usual.R.S.V. is increasingly recognized as a major respiratory threat, particularly to older adults, immunocompromised people and young children. “R.S.V. has a burden of disease similar to flu in older adults — it can make you very, very sick,” said Dr. Helen Chu, a physician and immunologist at the University of Washington.Scientists expect respiratory viruses to return to their prepandemic patterns eventually, but “it’s going to be unpredictable for the next two years,” Dr. Chu said.Which vaccines should I seek out?Everyone should have at least the flu and Covid shots this fall, experts said.The annual flu vaccine is recommended for everyone 6 months and older, but it is most important for adults aged 65 and older, children under 5 and people with weak immune systems.Updated Covid shots are coming this fall from Pfizer, Moderna and Novavax, and all are designed to target XBB.1.5, the Omicron variant that currently accounts for roughly 27 percent of cases. The full recommendations will not be available until the F.D.A. authorizes the shots and the C.D.C. reviews new data.Federal health officials aren’t talking about a primary series of shots followed by boosters. (Officials aren’t even calling the shots “boosters” anymore.) Instead, they are trying to steer Americans toward the idea of a single annual immunization with the latest version of the vaccine.“Like a seatbelt in a car, it’s a good idea to keep using it,” Dr. Camille Kotton, a physician at Massachusetts General Hospital and an adviser to the Centers for Disease Control and Prevention, said of the Covid vaccine.R.S.V. is a frequent cause of respiratory illness among older adults, particularly those 75 or older who have other conditions, such as cardiovascular disease, chronic lung disease or diabetes.The new R.S.V. vaccine is not approved for Americans younger than 60. The C.D.C. recommends that people aged 60 and older sign up for the shot after consulting with their doctors.While it’s true that risks posed by any of the three viruses increases with age, remember that “65 is not a magical cutoff point,” Dr. Chu said.“Even those with no pre-existing conditions can become quite sick with all three of these viruses,” she said.When should I get the vaccines?No one knows when these viruses will re-emerge, so you should get the shots early enough in the fall to build immunity against the pathogens. Most people will not want or be able to make multiple trips to a clinic or pharmacy to space the shots apart.That probably means September or October. Most Americans may want to consider receiving the flu and Covid shots at the same time, so they are prepared to face either virus. Older adults who are in poor health — who have heart or lung disease, for example, or are on home oxygen — should get all three shots, some experts said.They should “get them as quickly as possible and definitely before the season, and do it all at once,” Dr. Chu said.Adults 50 and older should also get the vaccine for shingles, if they haven’t already, and those 65 and older should sign up for the pneumococcal vaccine. But those vaccines don’t need to be given in the fall and should be scheduled for a different time, Dr. Chu said.Is it safe to get these vaccines at once?The flu and Covid shots were often given together last fall and seemed to work well. Because the R.S.V. vaccine is new, however, there is little information on how it might interact with the other two vaccines.“The available data pertaining to the administration of influenza and Covid-19 vaccines at the same time do not indicate safety concerns,” the Department of Health and Human Services said in a statement to The New York Times.“F.D.A. and C.D.C. systems monitor vaccine safety year round and will remain in place,” the department said. “If any new potential safety signals are identified, the F.D.A. and C.D.C. will conduct further assessment and inform the public.”Some research suggests that the R.S.V. and flu vaccines produce lower levels of antibodies when given together than when delivered one at a time. But those levels are probably still high enough to protect people from the viruses, experts said.There is also limited data on the safety of the two R.S.V. vaccines. Clinical trials recorded six cases of neurological problems, including Guillain-Barré syndrome, compared with none in the placebo groups.But the numbers were too small to determine whether the cases were a result of the inoculations. More clarity will come from surveillance while the vaccines are administered on a large scale, Dr. Chu said.The C.D.C. is expected to make recommendations on administration of the vaccines together in the coming weeks.